application of nanomaterials in medicine: drug delivery

Application of Nanomaterials in Medicine: Drug delivery, Diagnostics and Therapeutics


*Biswajit Saha PhD1, Manjusri Bal PhD2 1Department of Physiology, City College, 102/1, Raja Rammohan Sarani, Kolkata-700009, Calcutta University, India 2Department of Physiology, University of Calcutta, Kolkata-700009. West Bengal, India.

Feyman’s Nanotechnology has multiple applications in clinical research for diagnosis, as nanodrugs or medicine, drug delivery as therapeutics. It is an endeavor to present here, the many varieties of nanomaterials and their application in physiology and medicine. Nanoparticles such as silver, gold, copper, zinc, calcium, titanium, magnesium have shown antimicrobial activity. The nanoparticles become highly reactive due to their change in physicochemical properties i.e. high surface-area-to-volume ratio. Antimicrobial gold nanoparticles are used in drug and gene delivery systems. Light induced plasmonic heating of gold nanoparticles might be an excellent photothermal therapeutic approach against cancer cells, bacteria and parasites. Zinc oxide nanoparticles are antimicrobial, anticancer, anti-diabetic, and anti-inflammatory theranostic agents. They develop cytotoxicity to cancer cells by increased ROS formation; inducing cancer cell death via the apoptosis signaling pathway. They deliver cancer drug such as doxorubicin, paclitaxel, etc. Non-toxic titanium dioxide is used in human food, drugs, cosmetics and food contact materials. Cadmium nanoparticles in the form of Quantum Dots are semiconductor metalloid-crystal structures have the potential for cellular imaging, cancer detection and treatment, drug delivery, etc. Magnesium oxide nanoflakes have been developed as drug carriers. Carbon can be used as nanotube for drug delivery, diagnosis, and treatment of cancer due to their unique chemical, physical, and biological properties, nanoneedle shape, hollow monolithic structure, and ability to carry drugs on their outer layers. Exosomes are the new kind of nanomaterials (20-200 nm) present in blood, saliva, breast milk, and sperm. These nanovessicles/nanostructures are released from cells which carry biomolecular information (miRNA, mRNA, proteins) as exosomal cargo. Exosomes are used in theranostic applications.

Key Words: Gold nanoparticles, Zinc oxide nanoparticles, Quantum Dots, Magnesium oxide nanoflakes, Carbon nanotube, Exosomes, apoptosis, theranostic, doxorubicin, paclitaxel. INTRODUCTION Nanotechnology - the prelude: The concept of nanotechnology was first incorporated by the Nobel laureate Physicist Richard Phillips Feynman in 1959 in his book “There’s Plenty of Room at the Bottom”. Nanotechnology introduces a good platform to modify and develop the important properties of metal in the form of nanoparticles (NPs) having promising applications in diagnostics, biomarkers, cell-labeling, antimicrobial agents, drug delivery systems and nanodrugs for the treatment of various diseases (Marcato and Duran, 2008; Singh and Nalwa, 2011). Nanomaterials have been considered for use in the optical devices, superconductors, fuel cells, catalysts, biosensors,

drug and gene delivery and so on (Adibkia et al., 2007; Tiwari et al., 2011; Zinjarde, 2012; Bahrami et al., 2014). Nanomaterials as the novel drug delivery systems have also been applied to improve the physicochemical and therapeutic effectiveness of the drugs (Ravishankar and Jamuna, 2011; Marambio-Jones and Hoek, 2010; Adibkia et al., 2009). Over the past few years, various nano-sized antibacterial agents such as metal and metal oxide

*Corresponding Author: Biswajit Saha PhD, Department of Physiology, City College, 102/1, Raja Rammohan Sarani, Kolkata-700009, Calcutta University, India. E-Mail: [email protected] Co-Author 2Email: [email protected]

Vol. 2(1), pp. 017-043, June, 2020. © www.premierpublishers.org. ISSN: 2281 - 0986

Review Article

International Research Journal of Nanoscience and Nanotechnology


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nanoparticles of silver (Ag), silver oxide (Ag2O), titanium dioxide (TiO2), zinc oxide (ZnO), gold (Au), calcium oxide (CaO), silica (Si), copper oxide (CuO), and magnesium oxide (MgO) have been known to show antimicrobial activity (Azam et al., 2012; Besinis et al., 2014; Emami-Karvani and Chehrazi, 2011; Usman et al., 2013; Chen et al., 2013; Pal et al., 2007; Zarei et al., 2014). It has been known that carbon-based nanoparticles exhibit high antimicrobial activity as well. Early studies indicated that fullerenes, single-walled carbon nanotubes (SWCNTs) and graphene oxide (GO) nanoparticles showed potent microbicidal properties. These new allotropic types of carbon have been discovered in the last two decades, and, since then, they have used in many field of science (Cataldo and Da Ros, 2008; Wang et al., 2014; Sokolov and Stankevich, 1993). It has also been elicited that, the size and surface area of carbon nanomaterials are important parameters affecting their antibacterial activity; that is, increasing the nanoparticles surface area by decreasing their size lead to improving their activity for interaction with bacteria (Kang et al., 2008; Buzea et al., 2007). Generally, the antimicrobial activity of the nanoparticles depends on their composition, surface modification, intrinsic properties, and the type of microorganism (Buzea et al., 2007; Hajipour et al., 2012). It has been proposed that carbon-based nanomaterials cause membrane damage in bacteria due to an oxidative stress (Gurunathan et al., 2012; Shvedova et al., 2012; Vecitis et al., 2010; Manke et al., 2013; Pacurar et al., 2012). According to recent studies the physical interaction of carbon-based nanomaterials with bacteria, rather than oxidative stress, is the primary antimicrobial activity of these nanostructures (Manke et al., 2013; Kang et al., 2007). In fact, the interactions between bacterial cells and carbon-based nanomaterials play an important role in their antimicrobial mechanism (Yang et al., 2010). There is some evidence in the literature that the aggregation between bacterial cells and carbon nanomaterials cause direct contact between the cells and carbon nanomaterials which in turn lead to cell death (Kang et al., 2007; Yang et al., 2010; Murray et al., 2012). 1. Silver nanoparticles (Ag NPs): Antimicrobial agents. Silver in the form of various compounds and bhasmas (ash) have been used in Ayurveda to treat several bacterial infections since time immemorial. Antimicrobial effects of silver can be increased by manipulating their size at nano-level. Because of their change in physicochemical properties, Ag NPs have emerged as antimicrobial agents owing to their high surface-area-to-volume ratio and the unique chemical and physical properties (Kim et al., 2007). Ag NPs having size in the range of 10–100 nm showed strong bactericidal potential against both Gram-positive and Gram-negative bacteria (Morones et al., 2005). The

silver ions are highly reactive, and they bind to proteins followed by structural changes in the bacterial cell wall and nuclear membrane, which leads to cell distortion and death. They also inhibit the bacterial replication, by binding and denaturing bacterial DNA (Landsdown, 2002; Castellano et al., 2007). Silver ions react with thiol group of proteins, followed by DNA condensation resulting in the cell death (Feng et al., 2000). Various types of silver compounds that are used as antimicrobials from ancient times include silver nitrate, silver sulfadiazine, silver zeolite, silver powder, silver oxide, silverchloride and silver cadmium powder. Ag NPs are also termed as new-generation of antimicrobials (Rai et al., 2009). Yamanaka et al. (2005) confirmed that silver ions penetrate into the bacterial cells and affect the ribosomal subunit protein and some enzymes important for the bacterial cell. De Souza et al. studied the antimicrobial activity of 19 antibiotics in combination with the silver–water dispersion solution (15-nm-diameter Ag NPs clusters containing silver ions produced by an electrocolloidal silver process). They found that the multi-drug-resistant Escherichia coli, Salmonella typhi, Shigella flexneri, Staphylococcus aureus, and Bacillus subtilis are susceptible to amoxicillin and clindamycin. Interestingly, the combination of silver–water dispersion and amoxicillin or clindamycin showed an additive effect on S. aureus 6538 P strain, S. typhi, S. flexneri and B. subtilis, while combination of silver–water dispersion and amoxicillin showed antagonistic effect with methicillin-resistant S. aureus strain (MRSA) (De Souza et al., 2006). Duran et al. (2007) synthesized Ag NPs using fungus Fusarium oxysporum, Shahverdi et al. (2007) synthesized Ag NPs using Klebsiella pneumoniae and evaluated their antimicrobial activity alone and in combination with the antibiotics such as penicillin G, amoxycillin, erythromycin, clindamycin and vancomycin against S. aureus and E. coli. They observed a significant increase in antibacterial activity of antibiotics in the presence of Ag NPs, and there was highest synergistic activity of nanoparticles with erythromycin against S. aureus. Percival et al. (2007) reported that Ag NPs can be used as effective broad-spectrum antibacterial agents for both Gram-negative, of the genera (Acinetobacter, Escherichia, Pseudomonas, Salmonella and Vibrio) and Gram-positive, of the genera (Bacillus, Clostridium, Enterococcus, Listeria, Staphylococcus and Streptococcus) bacteria, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA). Factors influencing the bactericidal effect of Ag NPs are size, shape, concentration and dose. The size dependency of bactericidal potential of nanoparticles was studied by Panacek et al. (2006). They reported that the nanoparticles of size 25 nm possessed highest antibacterial activity. It was found that triangular


Int. J. Res. Nanosci. Nanotechnol. 19

nanoparticles are more active than spherical or rod-shaped nanoparticles against E. coli. (Pal et al., 2007). Hence, nanotechnology may provide a good platform to overcome the problem of antibiotic resistance, with the help of the Ag NPs. 2. Gold nanoparticles (Au NPs): antibacterial and anti-cancer theranostic agents. Gold nanoparticles (Au NPs) have been considered as the most interesting nanomaterial because of their unique optical, electronic sensing and biochemical properties. Au NPs have been potentially applied for medical imaging, drug delivery, tumor therapy, diagnosis, and treatment of diseases (Fen-Ying et al., 2017). 2a) Antibacterial activity of Au NPs: Au NPs have been proved to have antibacterial action. Zhou et al. (2012) demonstrated that gold and silver nanoparticles displayed excellent antibacterial potential for the Gram-negative bacteria E. coli and the Gram-positive bacteria BCG. Lima et al. (2013) reported that Au NPs dispersed on zeolites eliminated E. coli and S. typhi at short times. The bactericidal properties of Au NPs were influenced by the key parameters as the size and roughness of nanoparticles. The more active materials were pointed out Au-faujasite. Those materials contained particles sized 5 nm at surface and eliminated 90–95% of E. coli and S. typhi colonies. Green synthesis of metal nanoparticles is an important technique in improved methods of eco-friendly nanoparticles production. Rajeshkumar et al. (2013) synthesized gold nanoparticles by using marine brown algae Turbinaria conoides. The colour changes from brown to pinkish red confirmed the gold nanoparticles synthesis. The triangle, rectangle and square shaped and 60 nm average sized gold nanoparticles were observed by Scanning Electron Microscope (SEM). The antibacterial activity of gold nanoparticles showed maximum inhibition by Streptococcus sp. and medium range of inhibition by B. subtilis and K. pneumoniae. Mechanism of action of Au NPs: Cui et al. (2012) studied the molecular mechanism of action of a class of bactericidal Au NPs which showed potent antibacterial activities against multi-drug-resistant Gram-negative bacteria by transcriptomic and proteomic approaches. Gold NPs exert their antibacterial activities mainly by two ways: one is to collapse membrane potential, inhibiting ATPase activities to decrease the ATP level; the other is to inhibit the subunit of ribosome from binding to tRNA, affecting translation. The Au NPs are capable of attaching to the bacterial membrane by electrostatic interaction and disrupt its integrity (Tiwari and Soo Lee, 2013). Au NPs can generate

holes in the cell wall causing leakage of cell contents, and bind with the DNA, inhibiting transcription (Rai et al., 2010). Au NPs aggregate within bacterial biofilms and bind to their surfaces causing cell wall distortions which can be utilized to minimize treatment durations and side-effects of drugs (Zawrah and Abd El-Moez, 2011). Oxidative stress generated by free radical formation, that is, ROS, is triggered by nanotoxicity that leads to the death of bacterial cell (Dakrong et al., 2011). The interaction between ultra-small Au NPs (less than 2nm range) and bacteria likely induce a metabolic imbalance in bacterial cells resulting in an increase of intracellular ROS species production that culminated in death of the bacteria (Zheng et al., 2017). 2b) The use of Au NPs in drugs and gene delivery systems:

Au NPs have been extensively studied in biological and photothermal therapeutic applications (Pissuwan et al., 2006, 2008; Huang et al., 2008; Hu et al., 2006; Daniel and Astruc, 2003; Tong et al, 2009; Ghosh et al., 2008). The delivery of drugs with nanoparticles can result in higher concentrations than possible with normal drug delivery schemes (Chen et al., 2008) which, for example, could increase the overall efficiency of a drug used to destroy pathogenic cells. Furthermore, the unique chemical, physical, and photo-physical properties of Au NPs can be exploited in innovative ways to control the transport and controlled release of pharmaceutical compounds (Skirtach et al., 2006; Sershen et al., 2000). The release of a drug from Au NPs could proceed via internal stimuli (operated within a biologically controlled manner; such as pH or glutathione) or via external stimuli (operated with the support of stimuli-generating processes; such as the application of light) (Ghosh et al., 2008; Gupta et al., 2002). Generally, there are two types of targeting, designated as ‘active’ and ‘passive’. The term ‘passive targeting’ most commonly refers to the accumulation of nanoparticles or pharmaceutical substances at a specific site by physiochemical factors (e.g. size, molecular weight), extravasation, or pharmacological factors (Vasir et al., 2005). In the case of ‘active targeting’, the nanoparticle or drug molecule has been conjugated with a specific active molecule that binds to the desired target cells or tissues. For example, nanoparticles can be targeted to specific phagocytic cells (Pissuwan et al., 2007) or to tumors (Bhattacharya et al., 2007). In the case of nanoparticles, modification and functionalization of the surface of the nanoparticles play a major role in this kind of targeting. 2b i) Conjugation of Au NPs with therapeutics. It has been shown that conjugates of gold nanoparticles with antibiotics provide promising results in the treatment of intracellular infections (Saha et al., 2007; Gu et al., 2003). The involvement of gold nanoparticles in antibiotic therapy can evidently increase the efficiency of drug delivery to target cells in some cases, although this is not inevitably true (Rosemary et al., 2006; Burygin et al.,


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2009). In general, the amount of antibiotics used in therapy is much higher than the actual dose required for pathogenic destruction. The excess amount of antibiotics can cause adverse effects (Geller et al., 1986). Therefore, the conjugation of gold nanoparticles with antibiotics in combination with some type of targeting would be a possible way to improve antibiotic efficacy. Gold nanoparticles can be directly conjugated with antibiotics or other drug molecules via ionic or covalent bonding, or by physical absorption. For example, methotrexate has been conjugated to 13 nm colloidal gold (Chen et al., 2007). Methotrexate is an analogue of folic acid that has the ability to destroy folate metabolism of cells and has been commonly used as a cytotoxic anticancer drug. The carboxylic groups on the methotrexate molecule can bind to the surface of Au NPs after overnight incubation. It has been reported that the concentration of the methotrexate conjugated to gold nanoparticle is higher than that of the free methotrexate at the same volume. The cytotoxic effect of free methotrexate is about seven times lower than that of methotrexate conjugated to gold nanoparticles in the case of Lewis lung carcinoma cells (Chen et al., 2007). In another example, Saha et al. (2007) directly conjugated different antibiotics to non-functionalized spherical gold nanoparticles of about 14 nm diameter. The gold nanoparticles were conjugated to ampicillin, streptomycin, and kanamycin by physical means. The conjugated forms of the antibiotics were claimed to provide a greater degree of inhibition of the growth of bacteria than the free forms of the antibiotics. Moreover, the stability of the antibiotics after conjugation with gold was also higher than the unconjugated forms. However, the bluish color of the conjugates suggested that there was some aggregation after conjugation, a situation that other workers consider very deleterious (Burygin et al., 2009). Therefore, it can be stated that modification of the surface of the gold nanoparticles to prevent aggregation would improve the efficacy of such drug delivery systems further. 2b, ii) Surface modification of Au NPs for drug delivery: The surface chemistry of a nanomaterial plays an important role in the conjugation process between biomolecules and nanoparticles. Studies on methods to improve the biocompatibility, bio-stability, and water-solubility of gold-bioconjugates have been recently carried out by several groups. Several studies have highlighted the attractive properties of polymer-modified gold nanoparticles. For example, Liao and Hafner (2005) replaced the stabilizing surfactant bilayer surrounding gold nanorods using thiol-terminated methoxypoly(ethylene glycol) instead. This proved suitable for conjugation with anti-rabbit IgG via long chain hetero-bifunctional cross-linker. The amphiphilic characteristics of poly(ethylene glycol) (PEG) in particular ensures that particles coated with it have a high degree of biocompatibility and an affinity for cell membranes. The use of PEG to modify the surface of Au NPs strongly increases the efficiency of cellular uptake compared to unmodified Au NPs (Choi et al., 2003;

Paciotti et al., 2006). The use of polymers such as PEG also prevents the aggregation of the Au NPs in environments of high ionic strength and supports a longer circulation of the particles in vivo systems (Kommareddy and Amiji, 2007; Shenoy et al., 2006). An example of drug delivery using PEG-modified Au NPs is provided by Paciotti et al. (2004). In this study, Au NPs of 26 nm diameter were coated with a mixture of tumor necrosis vector and PEG-thiol and used to target tumor cells by extravasation. However, methods for actively targeting tumor cells with Au NPs are also available. For example Bhattacharya et al. reported that Au NPs functionalised with folic acid and PEG-amines by non-covalent interactions were readily targeted to the folate receptors of cancer cells. Conjugates of folic acid with Au NPs could have an important role for folate receptor-targeted drug delivery or targeted therapy in the future (Bhattacharya et al., 2007). The ‘layer-by-layer’ technique is another interesting way to modify the surface. Takahashi et al. (2008) used this technique to modify phosphatidylcholine-gold nanorods (PC-NR) with bovine serum albumin (BSA) and polyethylenimine (PEI). The BSA-PC-NRs were wrapped inside PEI after a layer-by-layer modification which increased the stability of gold nanorods in electrolyte buffer solution. This modification increased the cellular binding and uptake of the nanoparticles and also prevented their aggregation under physiological conditions. Gu et al. (2009) has demonstrated a new form of surface functionalized Au NPs that has the capability to target a payload to the cell nucleus. The surfaces of spherical Au NPs of 3.7 nm diameter were modified with 3-mercaptopropionicacid (MPA) to form a self-assembled monolayer. NH2-PEGNH2 was then conjugated to the MPA layer via amidation between the amine end-groups on the PEG and the carboxylic group on the Au NPs. This conjugation results in good stability in an electrolyte environment and a high efficiency of intracellular transport, both factors being useful for delivery targeted to the nucleus. Another recent example of a nano-sized drug delivery system consists of Au NPs functionalized with paclitaxel (Gibson et al., 2007). 2b, iii) Photothermal therapeutic strategy against cancer cells, bacteria and parasites: Light can be used as an external stimulus to release a drug from Au NPs. It is well known that Au NPs of various shapes can undergo a strong plasmon resonance with light (Pissuwan et al., 2006; Harris et al., 2006). Therefore, these nanoparticles have been considered for use in photothermal therapeutic programs directed at different types of target cells including cancers, bacteria and parasites (Pissuwan et al., 2006, 2007, 2009; Norman et al., 2007). In this context the use of Au NPs may be complementary to photodynamic therapy (PDT), in which



light is used to generate oxidizing oxygen species at a target site. Light-induced plasmonic heating may also be exploited to release a chemical payload which had been attached to the Au NPs. This might also provide an interesting approach to delivery material directly into the cytoplasm or nucleus of target cells. Photo-activated drug release by plasmonically active particles appears to have been first described in 2000 (Sershen et al., 2000; West and Halas, 2000) followed by a related US patent (West et al., 2002). These works exploited a polymer-gel permeated with gold nanoshells to control drug release. Shortly thereafter, Radt et al. (2004) used spherical Au NPs in a comparable role to achieve the light-induced bursting of lysozyme containing packages in order to destroy Micrococcus lysodeikticus. Although the plasmon resonance of the original spherical Au NPs is in the middle of the visible wavelength, the resonance peak

can be shifted to the near-infrared (NIR, ∼800–1200 nm) by using more complex shapes, for example gold nanorods or gold nanoshells. The use of these more complex nanoparticles could be valuable for in vivo therapy due to the increased transparency of body tissues at NIR wavelengths (Loo et al., 2004; O'Neal et al., 2004). Recent studies of photoreactions using gold nanorods with pulsed laser irradiation have demonstrated good control of the release of bound PEG (mPEG5000-SH) molecules (Yamashita et al., 2009). For example, about 65% of the PEG chains on the surface of gold nanorods were released after irradiation by a pulsed laser with 25 mJ/pulse. The PEG was liberated by three processes: cleavage of the Au–S bonds, fragmentation of the chains, and reduction in the surface area of the gold nanoparticle as it morphed from rod to sphere (Yamashita et al., 2009). A related development using gold nanorods coated with poly(N-isopropylacryamide)(PNIPAM) hydro gels has been reported by the same group. In this case, application of the NIR laser caused rapid shrinkage of the hydro gels and released the drug (Shiotani et al., 2007; Takahito et al., 2009). These studies support the idea of using Au NPs in an optically-controlled drug release system in the future. In an extension of these principles, Au NPs can be used as a substrate onto which a light-sensitive molecule can be attached. For example, spiropyran is a light-sensitive and fully reversible conformation-changing molecule. When it is irradiated by UV light, its conformation is changed from a closed form to an open form. The process can be reversed by the application of visible light or heat. The open form can construct complexes with amino acids but these complexes are destroyed when the molecule returns to its closed form. This results in release of the amino acids (Ipe et al., 2003). Such a conjugate could become the basis of an effective light-mediated, controlled release system to treat selected conditions. Although the optical properties of the gold nanoparticle itself are not exploited in this case, a light source is still needed to achieve the therapeutic effects (Thomas and Kamat, 2003). In another example of this principle, it has been

reported that PEGylated spherical gold nanoparticle conjugates could be bound to silicon phthalocyanine4 (Pc 4), a hydrophobic drug which is being considered for photodynamic therapy. The attachment is through N–Au bonding of the amine group on the Pc 4 axial ligand to the PEGylated gold surface (Cheng et al., 2008). After the PEGylated gold nanoparticle-Pc 4 conjugate attains the tumor site, irradiation with light of about 670 nm was used to liberate the Pc 4 molecules from the surface of the nanoparticle and initiate phototherapy. Accumulation of the Pc 4 was found at the tumor site only 2 h after injection. Normally it would about two days for the unconjugated Pc 4 molecule to reach the target site inappreciable proportions due to its hydrophobic nature (Cheng et al., 2008).NA 2b, iv) Application of Au NPs in gene delivery: Au NPs can also be used to carry nucleic acids (Felnerova et al., 2004). Generally, the use of nucleic acids to treat and control diseases is termed ‘gene therapy’. This type of therapy can be performed by using viral and non-viral vectors to transport foreign genes into somatic cells to rectify defective genes there or provide additional biological functions (Luo and Saltzman, 2000; Roy et al., 1999). The use of viruses as a vehicle for gene therapy is now well known (Yeh and Perricaudet, 1997), however, viral vectors have disadvantages such as irregular cytotoxicity, the stimulation of an immune response, limitations in targeting specific cell types, low DNA carrying capacity, lack of ability to infect non-dividing cells, and difficulties in production and packaging (Ghosh et al., 2008; Luo and Saltzman, 2000; Check, 2002; Crystal, 1995; Zhang and Godbey, 2006). Among other nanoparticles such as magnetic nanoparticles, carbon nanotubes and liposomes have been of great interest as non-viral carriers for gene delivery (Boyer et al., 2010; Gao et al., 2006; Suzuki et al., 2008; McIntosh et al., 2001). Au NPs are also attractive because of their unique properties. In 2001 there was an investigation of Au NPs that had been functionalized with cationic quaternary ammonium groups and then electrostatically bound to plasmid DNA. This composite particle could protect the DNA from enzymatic degradation and could regulate DNA transcription of T7 RNA polymerase (McIntosh et al., 2001; Han et al., 2006). Thereafter, the same group has also reported the release of DNA from the modified gold nanoparticle after treatment with glutathione (GSH) (Han et al., 2005). In another report, cationic Au NPs prepared by NaBH4 reduction in the presence of 2-aminoethanethiol formed a complex structure with plasmid DNA containing a luciferase gene (Niidome et al., 2004). This complex particle could be used to deliver a gene into the target HeLa cells in about 3 h. Gold nanorods also have the potential to deliver siRNA to target cells or tissues. The electrostatic binding of siRNA and gold nanorods has been


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recently reported by the Prasad group (Bonoiu et al., 2009). They conjugated cetyltrimethylammonium bromide (CTAB) gold nanorods to siRNA (against DARPP-32 gene in dopaminergic neuronal (DAN) cells) and studied the uptake of conjugates inside the DAN cells. Using both dark-field imaging and confocal microscopy, they found that the siRNA was efficiently delivered into DAN cells after treatment with the gold nanorod–siRNA conjugates and cell viability was 98%. Moreover, there was still about 67% knockdown of DARPP-32 gene expression after 120 h for the cells that were incubated with the gold nanorod–siRNA conjugates, compared to only about 30% knockdown for cells treated with a commercial transfection agent as a control. This study also confirms that gold nanoparticles can be used as innovative vehicle to deliver genes into neuron cells. According to the authors of that study, this might one day provide the basis for a nanotherapy to treat drug addiction in patients. Recent work has shown that the combination of phototherapy with conventional gene therapy offers a high possibility to improve the efficiency of gene delivery into cells (Mariko et al., 2005). For example, Niidome et al. (2006) have investigated the release of plasmid DNA from spherical gold nanoparticles after exposure to pulsed laser irradiation. Spherical gold nanoparticles were produced by a similar method (Niidome et al., 2004); but in this case polyethylene-glycol-orthopyridyl-disulfide (PEG-OPSS) was added before conjugation with plasmid DNA to increase the stability of the complex particle. The plasmid DNA was released from gold–DNA complex particles by laser irradiation at a power density value of80 mJ/pulse without any fragmentation of DNA. A controlled release system for genes using gold nanorods offers significant possibilities in gene therapy. Chen et al. (2006) have explored the remote control of green fluorescence protein (EGFP) expression in HeLa cells using gold nanorods excited with NIR irradiation. EGFP genes were attached to the surface of gold nanorods by linking of thiolated EGFP DNA through Au–S bonds. When femtosecond NIR irradiation was applied to the gold nanorod–EGFP DNA conjugates, a change of shape from rod to sphere was observed. It was proposed that the transformation of shape induced a release of DNA from gold nanorod–EGFP DNA conjugates. A similar phenomenon was described by the Yamada group (Takahashi et al., 2005). When NIR irradiation of nanorod–EGFPDNA conjugates had been performed in HeLa cells, the expression of EGFP in cells was detected at the irradiated spot after NIR exposure at79 μJ/pulse for 1 min. At this condition, around 80% of cells were still alive. Some other nanoparticles: Apart from Ag NPs, and Au NPs, antibacterial activity of other metal oxide nanoparticles viz. Al2O3, Fe3O4, CeO2, ZrO2, MgO against antibiotic resistant bacterial pathogens was investigated by Gokulakrishnan et al. (2012). It was

found that MgO nanoparticle showed maximum sensitivity against S. pneumoniae and showed minimum sensitivity against Klebsiella sp. 3. Copper nanoparticles (Cu NPs): antimicrobial agent. Copper is a readily available metal and one of the essential trace elements in most living organisms. This metal has been also used as potential antimicrobial agent since ancient times. Copper-containing compounds such as CuSO4 and Cu(OH)2 are used as the traditional inorganic antibacterial agents (Raffi et al., 2010). Also, aqueous copper solutions, complex copper species or copper containing polymers are used as antifungal compounds (Raffi et al., 2010). Moreover, the control of legionella in hospital water distribution systems via the copper and silver ionization method is one of the most common applications of this metal in the modern healthcare setting (O'Gorman and Humphreys, 2012). Copper ions have demonstrated antimicrobial activity against a wide range of microorganisms, such as E. coli, S aureus, Salmonella enterica, Campylobacter jejuni, and Listeria monocytogenes (Gyawali et al., 2011). Currently, copper has been registered as the first and only metal with antimicrobial properties by the American Environmental Protection Agency (EPA) (Prado et al., 2012). This material kills 99.9% of most pathogens within 2 h contact (Hans et al., 2013). Cu NPs showed higher antibacterial effect relative to the Ag NPs against E. coli and B. subtilis (Ruparelia et al., 2008; Yoon et al., 2007). The copper surfaces can be used to kill bacteria, yeasts, and viruses which are known as “contact killing” (contact-mediated killing). Contact killing by copper was reported to occur at a rate no less than seven to eight logs per hour, and in general, subsequent to the extended incubation. No live microorganisms were recovered from the copper surfaces. This leads to the idea of using copper as a self-sanitizing material (Grass et al., 2011). Maqusood et al. (2014), studied the structural and antimicrobial properties of copper oxide nanoparticles (CuO NPs) synthesized by a very simple precipitation technique. Copper (II) acetate was used as a precursor and sodium hydroxide as a reducing agent. X-ray diffraction patter (XRD) pattern showed the crystalline nature of CuO NPs. Field emission scanning electron microscope (FESEM) and field emission transmission electron microscope (FETEM) demonstrated the morphology of CuO NPs. The average diameter of CuO NPs calculated by TEM and XRD was around 23 nm. Energy dispersive X-ray spectroscopy (EDS) spectrum and XRD pattern suggested that prepared CuO NPs were highly pure. CuO NPs showed excellent antimicrobial activity against various bacterial strains (E. coli, P. aeruginosa, K. pneumonia, E. faecalis, S. flexneri, S. typhimurium, P. vulgaris, and S. aureus). Moreover, E. coli and E. faecalis exhibited the highest sensitivity to CuO NPs while K. pneumonia was the least sensitive (Maqusood et al., 2014).



Godymchuk et al. (2015), studied that the production of bactericidal plasters, bandages and medicines with the incorporation of copper nanoparticles and copper ions may have a great potential in terms of their biomedical application. The work considers the influence of the synthesis conditions, size, aggregation status, and charge of nanoparticles in aqueous solutions as well as the type of microorganisms to the antibacterial properties of water suspensions of electroexplosive copper nanoparticles in the conditions in vitro in relation to strains E. coli, P. aeruginosa, S. aureus, and B. cereus. The authors have demonstrated that use of deeply purified water and alcohol-containing stabilizers at the synthesis of nanoparticles via metals electric erosion in the liquid prevents the copper nanoparticles coagulation and significantly influences on their physicochemical characteristics and, consequently, antibacterial properties (Godymchuk et al., 2015). The toxicity mechanisms of Cu NPs against bacteria: One of the most known NPs' toxicity mechanisms is the interaction between the bacterial cell membrane and NPs, which leads to the disruption of the bacterial membrane integrity and finally results in the death of the microorganism. It has been shown that several factors, including temperature, pH, concentration of bacteria and NPs, as well as aeration can promote the toxicity mechanism of Cu NPs (Tiwari et al., 2008). Cu particles in nano-scale have been shown to have antibacterial effects on the bacterial cell functions in multiple ways, including adhesion to Gram negative bacterial cell wall due to electrostatic interaction, having effect on protein structure in the cell membrane, denaturation of the intracellular proteins, and interaction with phosphorus- and sulphur-containing compounds like DNA (Raffi et al., 2010). Also, in one comprehensive study, mechanisms of antibacterial activity of Cu NPs were investigated using E. coli as a biological tool (Chatterjee et al., 2014). The results showed that the treatment of E. coli cells by Cu-NPs at the minimum bactericidal concentration (MBC) resulted in 2.5 times overproduction of the cellular reactive oxygen species (ROSs). Also, the NP-mediated increase in ROS level led to noticeable lipid peroxidation, protein oxidation, DNA degradation and finally cell killing. 4. Zinc Oxide (ZnO) nanoparticles: Biological application. Role of ZnO NPs as antimicrobial, anticancer, antidiabetic, and antiinflammatory theranostic agents though Zn++ is indigenous to human body: ZnO NPs are the most important metal oxide nanoparticles. They have been used in various fields due to their peculiar physical and chemical properties (Smijs and Pavel, 2011; Ruszkiewicz et al., 2017). ZnO NPs are increasingly used in personal care products, such as cosmetics and sunscreen because of their strong UV

absorption properties (Newman et al., 2009), including antimicrobial properties. In the textile industry, the finished fabrics exhibited attractive functions of ultraviolet and visible light resistance, antibacterial, and deodorant by adding ZnO NPs (Hatamie et al., 2015). It is well known that zinc is present as an essential trace element in different organs including brain, muscle, bone, skin, and so on in humans. As the main component of various enzyme systems, zinc takes part in body’s metabolism and plays crucial roles in proteins and nucleic acid synthesis, hematopoiesis, and neurogenesis ( Smijs and Pavel, 2011; Ruszkiewicz et al., 2017; Kolodziejczak-Radzimska and Jesionowski, 2014; Sahoo et al., 2007). Nano-ZnO, with small particle size, makes zinc more easily to be absorbed by the body. Thus, nano-ZnO is commonly used as a food additive. Moreover, ZnO is graded as a “GRAS” (generally recognized as safe) substance by the US Food and Drug Administration (FDA) (Rasmussen et al., 2010). Compared with other metal oxide NPs, ZnO NPs are cheap and less toxic. They can be applied as antioxidant, antibacterial, anticancer, anti-diabetic, anti-inflammatory agents including drug delivery, wound healing, and bioimaging (Rasmussen et al., 2010; Mishra et al., 2017; Zhang and Xiong, 2015; Kim et al., 2017; Xiong, 2013). ZnO NPs less than 100nm are considered to be relatively biocompatible, which support their biomedical applications and represent a powerful property. 4, a) Anticancer property of ZnO NPs: Zn2+ is an essential nutrient for adults, so ZnO NPs are safe in vivo. ZnO NPs can be introduced as biocompatible and biodegradable nanoplatforms for cancer treatment (Zhang et al., 2013; Martinez-Carmona et al., 2018). The mitochondrial electron transport chain is known to be associated with intracellular ROS formation. Anticancer agents entering into cancer cells could destroy the electron transport chain and release huge amounts of ROS (Stowe and Camara, 2009; Moghimipour et al., 2018). Excessive ROS produces mitochondrial damage and loss of protein activity that finally causes cell apoptosis (Guo et al., 2013). ZnO NPs become cytotoxic to cancer cells by releasing dissolved zinc ions, followed by increased ROS induction and cancer cell death via the apoptosis signaling pathway. The effects of ZnO NPs on human liver cancer HepG2 cells and its possible pharmacological mechanism were reported by Sharma et al. (2012). ZnO NPs-exposed HepG2 cells showed higher cytotoxicity and genotoxicity, resulting cell apoptosis mediated by the ROS. Biosynthesis of ZnO NPs was performed by Moghaddam et al. (2017) using a new strain of yeast (Pichia kudriavzevii GY1). They evaluated the anticancer activity of ZnO NPs in breast cancer MCF-7 cells. ZnO NPs showed powerful cytotoxicity against MCF-7 cells, associated with the occurrence of apoptosis. The ZnO


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NPs-induced apoptosis was mainly through both extrinsic and intrinsic apoptotic pathways, and some anti apoptotic genes of Bcl-2, AKT1, and JERK/2 were down regulated, while proapoptotic genes of p21, p53, JNK, and Bax were upregulated. ZnO NPs have been widely used in cancer therapy because they have cytotoxic effect on cancer cell proliferation. It has been found that ZnO NPs could be more cytotoxic to cultured C2C12 myoblastoma cancer cells than 3T3-L1 adipocytes. Compared to 3T3-L1 cells, it appeared that ZnO NPs inhibited C2C12 cell proliferation and caused a marked apoptosis via a ROS-mediated mitochondrial intrinsic apoptotic pathway and p53, Bax/Bcl-2 ratio, and caspase-3 pathways (Chandrasekaran and Pandurangan, 2016). ZnO NPs with a crystal size of 20nm produced concentration-dependent loss of ovarian cancer SKOV3 cell viability (Bai et al., 2017). ZnO NPs were made by Arakha et al. (2017) using the chemical precipitation method. They evaluated their anticancer activity, and found that ZnO NPs with different sizes could obviously inhibit the proliferation of fibrosarcoma HT1080 cells. It was an evidence of the occurrence of autophagy in cancer cells which was related to intracellular ROS generation. Zhang et al. (2017) explored the regulatory mechanism of autophagy and the relation between autophagy and ROS in ZnO NPs-treated lung epithelial cells. The results showed the ZnO NPs induced accumulation of autophagosomes and impairment of autophagic flux in A549 cells. zinc ions released from ZnO NPs were able to damage lysosomes, leading to impaired autophagic flux and mitochondria. Impaired autophagic flux resulted in the accumulation of damaged mitochondria, which could generate excessive ROS to cause cell death. 4a, i) Drug delivery for cancer treatment: Targeted drug delivery with the help of ZnO NPs provides excellent opportunities for much more safety and effective cancer treatment. By targeting the actual sites of cancer cells, nanoparticle-based delivery could minimize the quantity of drugs and undesirable side effects (Rasmussen et al., 2010; Erathodiyil and Ying, 2011). ZnO NPs in comparison to other nanomaterials, are safe due to their low toxicity and biocompatibility. Researchers have explored ZnO NPs as multi-target and multifunctional anticancer nanomedicine. Different varieties of drugs such as doxorubicin, paclitaxel, curcumin, baicalin or DNA fragments could be loaded onto the ZnO NPs for better solubility, higher toxicity than individual agents, and effective delivery into the cancer cells (Puvvada et al., 2015; Wang et al., 2017; Ghaffari et al., 2017; Li et al., 2017).

Hariharan et al. (2012) synthesised PEG 600 modified ZnO NPs (ZnO/PEG NPs) by coprecipitation technique, following the loading of doxorubicin (DOX) to form DOX-ZnO/PEG nanocomposites. DOX-ZnO/PEG nanocomposites improved intracellular accumulation of DOX resulting a concentration dependent inhibition on cervical cancer HeLa cell proliferation. Deng and Zhang (2013) prepared ZnO nanorods using chemical precipitation method for carrying Dox to construct a Dox-ZnO nanocomplex. After culture with SMMC-7721 hepatocarcinoma cells, Dox-ZnO nanocomplexes were used as an efficient drug delivery system for transporting Dox into SMMC-7721 cells and enhancement of the cellular uptake of Dox. Moreover, ultraviolet (UV) exposed Dox-ZnO nanocomplexes destroyed more cells through photocatalytic properties, and synergistically triggered caspase-dependent apoptosis. A new ZnO hollow nanocarrier (HZnO) was prepared by engineering surface with biocompatible substrates following conjugation with targeting agent folic acid (FA) and loaded with paclitaxel (PAC) to designate as the FCP-ZnO nanocomplex (Puvvada et al., 2015). The folate receptors are over expressed in the breast cancer MDAMB- 231 cells. FCP-ZnO nanocomplexes accumulated increasingly in MDAMB- 231 cells. Due to FA-mediated endocytosis and intracellular release within the acidic endolysosome, the FCP-ZnO nanocomplexes not only exhibited significantly higher cytotoxicity in vitro MDA-MB-231 cells but also reduced MDA-MB-231 xenograft tumors in nude mice. 4, b) Antibacterial action of ZnO NPs: ZnO NPs can be chosen as antibacterial agent because of their great properties, such as high specific surface area and high activity to block wide range of pathogenic agents. The main antibacterial toxicity mechanisms of ZnO NPs are based on their ability to induce excess ROS generation, such as superoxide anion, hydroxyl radicals, and hydrogen peroxide production (Zhang and Xiong, 2015). The antibacterial action takes place due to accumulation of ZnO NPs in the outer membrane or cytoplasm of bacterial cells, triggering Zn2+ release, resulting bacterial cell membrane disintegration, membrane protein damage, genomic instability, and finally, killing of bacterial cells (Shi et al., 2014; Jiang et al., 2016; Dutta et al., 2013). Presently, Gram-negative E. coli and Gram-positive S. aureus are mainly chosen as model bacteria to evaluate the antibacterial activity of ZnO NPs (Dutta et al., 2013; Reddy et al., 2007). Some other Gram-negative bacteria such as P. aeruginosa (Singh et al., 2014), P. vulgaris (Ishwarya et al., 2018), V. cholerae (Chatterjee et al., 2010), and other Gram-positive bacteria such as B. subtilis (Hsueh et al., 2015) and E. faecalis (Divya et al., 2018) are also investigated.



The mechanism of antibacterial action of ZnO NPs against E. coli was reported by Jiang et al. (2016). ZnO NPs with an average size about 30nm destroyed cells by directly contacting with the phospholipid bilayer of the membrane, disrupting the membrane integrity. ROS production played a necessary function in the antibacterial properties of ZnO NPs. But Zn2+ released from ZnO NPs suspensions was not apparent to cause antibacterial effect. Reddy synthesized ZnO NPs with sizes of ~ 13nm and tested their antibacterial activities against E. coli and S. aureus (Reddy et al., 2007). It was observed that ZnO NPs inhibited the growth of E. coli at concentrations of about 3.4mM and of S. aureus at much lower concentrations (≥1 mM). It was also reported that the antibacterial activity of ZnO NPs with small crystallite sizes was stronger than those with large crystallite sizes against E. coli and S. aureus (Ohira and Yamamoto, 2012). The amount of Zn2+ released from the small ZnO NPs were much higher than large ZnO powder sample and E. coli was more sensitive to Zn2+ than S. aureus. So it can be concluded that eluted Zn2+ from ZnO NPs play a key role in antibacterial action. Crustacean immune molecule β-1,3-glucan binding protein (Phβ-GBP) was extracted from the haemolymph of Paratelphusa hydrodromus by Iswarya et al. (2017) which were used for the creation of the Phβ-GBP-coated ZnO NPs. The Phβ-GBP-ZnO NPs were 20–50 nm in size and spherical in shape prevented the growth of S. aureus and P. vulgaris. Gram-negative bacterium V. cholerae causes epidemic disease cholera, a serious diarrheal disorder due to intestinal infection affects populations in the developing countries (Chatterjee et al., 2010; Salem et al., 2015). Sarwar et al. (2016) was looking for a nanomedicine against cholera. They have studied the effect of ZnO NPs against V. cholerae having two biotypes classical and El Tor. ZnO NPs was found to be more effective in inhibiting the growth of El Tor (N16961) biotype of V. cholerae, associated with ROS production, resulting bacterial membrane damage, increasing permeabilization and substantial modification of their morphology. The antibacterial activity of the ZnO NPs was found in cholera toxin (CT) mouse models. It was found that ZnO NPs could induce modification of the CT secondary structure and interruption of CT binding with the GM1 ganglioside receptor (Sarwar et al., 2017). Among six metal oxide nanoparticles ZnO NPs have highest antibacterial effects against S. aureus (Jones et al., 2008). ZnO NPs can be used as antibacterial agents in ointments, lotions, and mouthwashes. It can also be added with various substances to prevent bacteria from adhering, spreading, and breeding in medical devices. 4, c) Application of ZnO NPs as antidiabetic agent: Diabetes mellitus is a serious public health problem. According to WHO’s estimation in 2014, more than 400

million people were suffering from diabetes round the globe (Seclen et al., 2017). Diabetes is caused due to incapability of insulin production or ineffective use of insulin produced (Nazarizadeh and Asri-Rezaie, 2016; Umrani and Paknikar, 2014). Zinc is a trace element present in all human tissues and tissue fluids. Zinc is required for maintenance of the structural integrity of insulin and plays important role in the synthesis, storage, and secretion of insulin from pancreatic beta cells (Malizia et al., 1998). Therefore, ZnO NPs have antidiabetic potential. Natural extract of red sandalwood (RSW) conjugated ZnO NPs was used by Kitture et al. (2015) as an effective antidiabetic agent. The antidiabetic activity was determined by α-amylase and α glucosidase inhibition assay with murine pancreatic and small intestinal extracts. ZnO-RSW conjugate showed moderately higher percentage of inhibition (20%) against porcine pancreatic α-amylase and more against murine pancreatic glucosidase than any one separate element of RSW and ZnO NPs. The conjugated ZnO-RSW inhibited glucosidase by 61.93% while ZnO NPs and RSW showed inhibition of 21.48% and 5.90%, respectively. Nazarizadeh and Asri-Rezaie (2016) compared the antidiabetic activity and oxidative stress of ZnO NPs and ZnSO4 in diabetic rats. They observed that ZnO NPs having small dimensions showed greater antidiabetic effect at higher doses (3 and 10 mg/kg) compared to ZnSO4 (30 mg/kg). As a result, blood glucose level was highly reduced and insulin level increased with improved serum zinc status in a time- and dose-dependent manner. Oxidative stress particularly at higher doses was also observed including high malondialdehyde production. The hyperglycemia state can induce inflammatory reaction by regulating C-reactive protein (CRP) and cytokines, such as interleukins, responsible for the development of cardiovascular diseases. ZnO NPs were fabricated using hydroxyl ethyl cellulose as a stabilizing agent for the alleviation of diabetes (Hussein et al., 2018). The inflammatory markers, interleukin-1 (IL-1α) and CRP level markedly decreased after ZnO NPs treatment, associated with an increase in nitric oxide (NO) and serum antioxidant enzyme (PON-1) levels in diabetic rats. 4, d) Role of ZnO NPs against inflammation: Inflammation is a kind of reaction in which physiological, immunological and biochemical reactions jointly participated in the body tissue against harmful stimuli, such as pathogens, damaged cells, or irritants (Ferrero-Miliani et al., 2006). Atopic dermatitis (AD) is an inflammatory skin disorder characterized by the damage of the skin involving complex interaction between genetic and environmental factors (Boguniewicz and Leung, 2011; Toncic and Marinovic, 2016). Human skin comes in the most intimate contact with


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the textiles for a long duration. ZnO functionalized textile fibers play very important role in the control of oxidative stress in AD in vitro and in vivo (Wiegand et al., 2013). It was reported that AD pruritus improved remarkably when AD patients wore the ZnO textiles overnight on 3 consecutive days. This might be due to having antioxidant and antibacterial potential of the ZnO textiles. It was observed by Ilves et al. (2014) that only nanosized ZnO (nZnO) could penetrate the deep layers of the allergic skin, but bulksized ZnO (bZnO) stayed in the upper layers of both damaged and allergic skin in the mouse AD model. In comparison to bZnO, nZnO showed higher anti-inflammatory response by decreasing proinflammatory cytokines (IL-10, IL-13, IFN-c, and 2 cytokines) in the mouse model of AD. It can be concluded from these results that ZnO NPs having small size were highly effective on reducing skin inflammation in AD models. Other than atopic dermatitis treatment ZnO NPs were also very effective for other inflammatory diseases. Nagajyothi et al. (2015) demonstrated a cheap and biocompatible anti-inflammatory activity of ZnO NPs using the root extract of P. tenuifolia. The anti-inflammatory activities were investigated in LPS-stimulated RAW 264.7 macrophages. ZnO NPs exerted remarkable anti-inflammatory action by dose-dependent suppression of NO production as well as the related protein expressions of iNOS, COX-2, IL-1β, IL-6, and TNF-α. Photo-mediated synthesis of ZnO NPs using the aqueous extracts of two mangrove plants, Heritiera fomes and Sonneratia apetala, was carried out by Thatoi et al. (2016). They noticed that ZnO NPs’ anti-inflammatory potential (79%) was higher than Ag NPs (69.1%). 4, e) Use of ZnO NPs for bioimaging: ZnO NPs revealed efficient blue emissions and near-UV emissions, having green or yellow luminescence related to oxygen vacancies, which could be applied in bioimaging field (Xiong, 2013; Zhang et al., 2013; Zhu et al., 2016). 5. Titanium dioxide TiO2 nanoparticles: Nontoxic TiO2 can be used in human food, drugs, cosmetics, and food contact materials. Haghi et al. (2012) reported, antibacterial effect of TiO2 nanoparticles on pathogenic strain of E. coli. Liquid and nutrient agar medium were used for E.coli culture and different antibiotics were used for disc diffusion technique to evaluate antibiotic resistance pattern of E.coli. Antibacterial effect of 0.01, 0.5, 1 and 1.5% of nano-TiO2 evaluated via optical density (OD) and Kirby-Bauer disc diffusion test. The E. coli strain was resistant to all antibiotics used in this study. Decrease of optical density (0.225, 0.218, 0.158, 0.075, 0.031 respectively) was

observed with the increase of nano-TiO2 concentration. Inhibition zone measurement showed the similar results. The maximum inhibition zone (5mm) was observed in 1.5% of nano-TiO2. Nanomaterials are known to inactivate cellular enzymes and DNA by binding to electron-donating groups such as Carboxylates, Amides, Indoles, Hydroxyls, Thiols, and etc. They cause little pores in bacterial cell wall, leading to increased permeability and cell death (Haghi et al., 2012). TiO2 is nontoxic and the American Food and Drug Administration (FDA) has approved TiO2 for use in human food, drugs, cosmetics, and food contact materials. The photocatalytic reaction of TiO2 has been used to inactivate a wide spectrum of microorganisms (Long et al., 2014; Altin and S¨okmen, 2014; Gupta et al., 2013). The bactericidal and fungicidal effects of TiO2 on E. coli, S. aureus, and Pseudomonas putida have been widely reported (Bonetta et al., 2013; Yao and Yeung, 2011). The development of TiO2-coated or incorporated food packaging has also received attention (Zhou et al., 2009; Luo et al., 2013; Gumiero et al., 2013; Chawengkijwanich and Hayata, 2008). Arora et al. (2015) tried to evaluate the inhibition effectiveness of titanium dioxide nanoparticles in combination with cell wall active antibiotics – ceftazidime and cefotaxime against the multi-drug resistant P. aeroginosa isolated from pus, sputum, endo-tracheal tract and broncho-alveolar lavage. Commercial Degussa-P25 TiO2 nanoparticle, antibiotics ceftazidime and cefotaxime were used in this study against multi-drug-resistant nosocomial pathogen. The nanoparticle showed antimicrobial effect on the pathogen at concentrations more than 350 mg/mL, when exposed to ultraviolet (UV) light for an hour. Minimum inhibitory concentration values obtained for the antibiotic cefotaxime were sixfolds higher than the antibiotic ceftazidime. They also reported that when those antibiotics were used in combination with UV-irradiated metal nanoparticle, ceftazidime resulted in enhanced antimicrobial activity whereas cefotaxime did not show any change (Arora et al., 2015). Recent uses of titanium dioxide (TiO2) have involved various applications which include the food industry. Othman et al. tried to develop TiO2 nanoparticle-coated film for potential food packaging applications due to the photocatalytic antimicrobial property of TiO2. The TiO2 nanoparticles with varying concentrations (0–0.11 g/ 100mL organic solvent) were coated on food packaging film, particularly low density polyethylene (LDPE) film. The antimicrobial activity of the films was investigated by their capability to inactivate E. coli in an actual food packaging application test under various conditions, including types of light (fluorescent and ultraviolet (UV)) and the length of time the film was exposed to light (one–three days).The antimicrobial activity of the TiO2 nanoparticle-coated films exposed under both types of lighting was found to increase with an increase in the TiO2 nanoparticle concentration

https://www.researchgate.net/scientific-contributions/2087941073_Z-S_Luo?_sg%5B0%5D=BN963Fo382ZFAoQ9jKzZw6zp_BBMdXXu1QwEROIwAwFg_ZK0UJuxSBgiYSuONvbWx-P0H9Y.xYkWVsKzyhJUu4opXyxGnWqsIkkD-S9ui-PK-CAQ6ITrtN6v0vzcx6WWC_OtTpN9ElSAD5aI0DJmPhpdf-Z7cQ&_sg%5B1%5D=FU_hFf5VCm4QUBleDA8vL9LAjT5-Zk678Vzn_A_Oh6xvVaViAUIqSrbsghxSjz6rqBjOZxI.8Yrzcunc2gwTbm82MzV49ZJgBkt3Gz5tZMOjHO4KU_H9VVYoYVLiN6b4jsFA0McG-wX3H21pL9H2L6Qprx590g



and the light exposure time. It was also observed that the antimicrobial activity of the films exposed under UV light was higher than that under fluorescent light. The developed film has the potential to be used as a food packaging film that can extend the shelf life, maintain the quality, and assure the safety of food (Othman et al., 2014). 6. Cadmium oxide (CdO) nanoparticles: Salehi et al proposed to use CdO NPs in elimination of environmental bacteria resistant to traditional antibiotics. In their study they have found that with the elevation in CdO NPs concentration, the antimicrobial property augments and the growth rate of S. aureus declines (Salehi et al., 2014). The development of cadmium-containing nanoparticles, known as quantum dots, show great promise for treatment and diagnosis of cancer and targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting. However, information on pharmacology and toxicology of quantum dots needs much further development, making it difficult to assess the risks associated with this new nanotechnology (Rzigalinski and Strobl, 2009).

6, a) Cadmium Nanoparticles --- Quantum Dots: In nanotechnology, cadmium is primarily utilized in the construction of particles known as quantum dots (QDs), which are semiconductor metalloid-crystal structures of approximately 2 – 100 nm, containing about 200-10,000 atoms (Smith et al., 2008; Juzenas et al., 2008). Due to their small size, QDs have unique optical and electronic properties that impart the nanoparticle with a bright, highly stable, “size-tunable” fluorescence. The large surface area imparted by small size also makes QDs readily able to be functionalized with targeting ligands for site-directed activity. Based on these properties, QDs have the potential for revolutionizing biological imaging at the cellular level, cancer detection and treatment, radio- and chemo sensitizing agents, and targeted drug delivery; and are the subject of several excellent reviews (Smith et al., 2008; Juzenas et al., 2008; Alivisatos, 2004; Hardman, 2006). However, enthusiasm for QDs is somewhat diluted by the fact that QDs contain substantial amounts of cadmium in a highly reactive form, and we know little about the health risks of exposure to cadmium nanoparticles. 7. Calcium oxide nanopparticles (CaO NPs): Antimicrobial action and synaphic delivery of drugs. Among inorganic nano metal oxide nanoparticles, CaO NPs have some distinct features. They have potential applications in food, environment and healthcare (Bae et al., 2006). CaO NPs possess excellent antimicrobial potential and capability to inactivate microbial endotoxin (Wang et al., 2017; Sawai, 2003). Due to CaO NPs unique

structural and optical properties they can be used as a potential drug delivery agent (Butt et al., 2015), in photodynamic therapy (PDT), photo-thermal therapy (PTT), and synaphic delivery of chemotherapeutic agents (Gedda et al., 2015). CaO NPs are safe material to human beings and animals. Calcium oxide NPs has significant consideration due to its histocompatibility and antimicrobial potential (Leonardo et al., 2006; Mohammadi and Dummer, 2011), tissue dissolution (Hasselgren et al., 1988), and capability to inactivate microbial endotoxin (Safavi and Nichols, 1993; Tanomaru et al., 2003). It exhibits cubic lattice showing anisotropic catalytic behavior and used as dopant to stabilize metal-oxide. Few research groups reported the synthesis of nano-CaO by using thermal decomposition and sol-gel techniques (Nirmala and Suresh, 2013). 8. Magnesium oxide nanoparticles (MgO NPs):MgO nanoflakes as cancer drug carrier. MgO NPs have been reported to inhibit gram-positive, gram-negative, and endospore-forming bacteria (Sawai et al., 2000; Jin and He, 2011; Stoimenov et al., 2002; Krishnamoorthy et al., 2012; Wetteland et al., 2016). Tang and Lv (2014) have reviewed MgO NPs as antibacterial agent. In order to take full advantage of MgO NPs toward potential clinical translation to broad medical applications, a consistent method was established by Nguyen et al. (2018) in their study and used to determine the efficacy of MgO NPs against different microorganisms. Under the consistent conditions, they investigated and directly compared the effects of MgO NPs on nine different types of pathogenic microorganisms in planktonic forms or biofilms, including gram-negative bacteria, gram-positive bacteria, yeasts, and their resistant strains (Nguyen et al., 2018). This is the first study to use the same well-defined and consistent method to quantify and directly compare antimicrobial activities of MgO NPs against five major infectious bacteria with drug resistant strains, four yeasts with drug resistant strains, and nascent biofilms (Nguyen et al., 2018). This was the first time also to study the activity of MgO NPs against Candida glabrata (C. glabrata), an organism that has been gaining resistance to multiple widely-used antifungals (Healey et al., 2016). Doxorubicin (DOX) is an anticancer drug commonly used in treating cancer; however, it has severe cytotoxicity effects. To overcome both the adverse effects of the drug and mineral deficiency (i.e., hypomagnesemia) experienced by cancer patients, Ranathunge et al (2019) have developed magnesium oxide (MgO) nanoflakes as drug carriers and loaded them with DOX for use as a targeted drug delivery (TDD) system for potential application in cancer therapy. They have reported the synthesis of flake-shaped MgO nanoparticles with narrow particle size distribution. Nanoflakes agglomerate to form self-assembled structures with 50% porosity (Ranathunge et al., 2019).


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Drugs such as DOX readily bind to the surfaces of these nanoflakes via hydrogen bonding and through electrostatic interactions. The inter-particle spaces of agglomerated nanoflakes can be filled up to 90.0% (loading capacity) with 92.4% drug loading efficiency. All materials synthesized were appropriately characterized by several independent analytical techniques with closely parallel results. The cumulative release kinetics of the drug was investigated at different pH values. Results corroborate the development of a novel material for loading DOX for pH dependent TDD to potentially treat both hypomagnesemia and cancer (Ranathunge et al., 2019). 9. Carbon nanotubes: Drug delivery and thermal treatment of cancer. Nanomaterials such as carbon nanotubes (CNTs), have unique properties that can be used for diagnostic purposes, thermal ablation, and drug delivery in cancer. CNTs are tubular materials having diameters in nanometer and axial symmetry. Therefore, they are applicable for cancer theranostics. Besides these, CNTs have the potential to deliver drugs directly to the targets (Madani et al., 2011). Surgical removal, chemotherapy, and radiotherapy, or, a combination of these three modalities are the only measures for cancer treatment (Utreja et al., 2010). Though there are improvements in the procedure of treatments over the last few years, the majority of conventional chemotherapeutic agents creates serious problems, such as destruction or malfunction of neighboring cells including the risks of systemic and cellular toxicity to nephrons, neurons, infertility, and thromboembolic complications, as well as the more common side effects, such as hair loss, nausea, and myocardial infarction. Inability of drugs to access tumor sites specifically, and difficulty in clinical administration of drugs are the problems of conventional chemotherapeutic treatment of cancer (Batra et al., 2009). For these reasons, destruction of cancer cells with minimum harm to normal body tissue has been the principal research area explored by investigators (Dhar et al., 2008) including the delivery of high doses of drug molecules to tumor sites for maximum treatment efficacy (Liu et al., 2008). Over the last few years, different biological nanomaterials (Ghanbari et al., 2011) have been developed due to the progress in synthetic chemistry, which can be applied in drug delivery, cancer diagnosis, treatment, and imaging. These nanomaterials include carbon nanotubes (CNTs), quantum dots (Jamieson et al., 2007), dendrimers, liposomes (Tan et al., 2010), and micelles (Chang and Prakash, 2001). 9, a) CNTs as drug carriers: CNTs have been recognized as one of the most promising nanomaterials for a variety of biomedical applications due to presence of unique properties (Sahoo et al., 2011).

Compared with other nanomaterials, CNTs are found to be more dynamic in their biological application. For example, quantum dots are used only in cancer cell imaging, but CNTs have the potential for imaging as well as for drug delivery and thermal ablation (Utreja et al., 2010). The principal area of interest for researchers has been application of CNTs in the delivery of drugs to their site of action. This is mainly because of their characteristics such as unique physical, chemical, and biological properties, nanoneedle shape, hollow monolithic structure. Besides these, they have ability to obtain the desired functional groups on their outer layers (Sahoo et al., 2011). Due to their unique shape they enter the cell via different methods, such as passive diffusion across the lipid bilayer, or endocytosis. CNT attaches to the surface of the cell and is subsequently engulfed by the cell membrane (Sahoo et al., 2011; Lamprecht et al., 2009). CNTs become promising drug carriers because of their hollow monolithic structure and their ability to bind desired functional groups. They can be functionalized to increase their solubility in water and stability in serum, having low toxicity at the cellular level (Sahoo et al., 2011; Beg et al., 2011). Different methods have been explored to elucidate the mechanism of cellular uptake of CNTs. Researchers investigated the movement of CNTs by labeling with fluorescent materials, such as quantum dots (Raffa et al., 2010). In addition, detection of CNTs by nonlabeling procedure has also been carried out by transmission electronic microscopy and atomic force microscopy (Sahoo et al., 2011; Porter et al., 2007). Atomic force microscope has some advantages, because it can operate in liquid form, and allow measurement under near physiological conditions (Lamprecht et al., 2009). Biological molecules are attached to CNTs by different methods. Drugs and biological molecules can be joined to the surface with the help of functional groups or be loaded inside the CNTs. These methods are termed as wrapping or filling modes of binding, respectively (Arsawang et al., 2011).

9, b) Classification of CNTs: CNTs are well ordered, hollow, carbon graphitic nanomaterials with high surface area, and ultralight weight (Sahoo et al., 2011). CNTs are classified as two varieties i.e. single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs). SWCNTs are composed of a single cylindrical carbon layer with a diameter in the range of 0.4–2 nm (Klumpp et al., 2006), depending on the temperature at which they have been synthesized. It has been noticed that at high temperature they become large in diameter. MWCNTs are made up of several cylindrical carbon layers having inner tubes with diameters in the range of 1–3 nm and outer tubes with diameters in the range of 2–100 nm (Bekyarova et al., 2005).



The basic carbon arrangement of SWCNTs is different from that of MWCNTs. The structure of SWCNTs is arranged in armchair, zigzag, chiral, or helical pattern. On the other hand, the structure of MWCNTs is divided in two types according to the pattern of the graphite sheets (Danailov et al., 2002). 9, c) Synthesis and properties of CNTs: CNTs can be synthesized by heating carbon black and graphite in a controlled flame. The disadvantage of this method is the irregularity in size, shape, mechanical strength, quality, and purity of the CNTs (Beg et al., 2011). Different types of CNTs with different properties are obtained depending on the type of synthesis (Klumpp et al., 2006; Ebbesen and Ajayan, 1992). Depending on application of the CNTs appropriate fabrication technique can be followed. For example, for electric transport, only SWCNTs should be used rather than MWCNTs; because SWCNTs can act either as semiconductor or metal whereas MWCNTs act as semiconductor only (Klumpp et al., 2006). SWCNTs are more efficient than MWCNTs in drug delivery. This is due to the one-dimensional structure of the SWCNT and efficient drug-loading capacity because of its ultrahigh surface area (Feazell et al., 2007). SWCNT-anticancer drug complex has longer blood circulation time than the anticancer drug alone, which can lead to more prolonged and sustained delivery of the drug to the tumor cells via the enhanced permeability and retention effect (Liu et al., 2008). once the functionalized SWCNT releases the drug into the targets, it is gradually excreted from the body via the biliary pathway and finally in the feces (Liu et al., 2008). It can be concluded that SWCNTs are suitable candidates for drug delivery and a promising nanoplatform for future cancer therapeutics. 9, d) Use of SWCNTs for imaging: SWCNTs can also be used for imaging. Single-molecule fluorescence spectroscopy and Raman spectroscopy techniques can be used to analyze the fluorescence and structural properties of SWCNTs. Fluorescence spectra from individual nanotubes with identical structures have different emission energies and line widths that likely arise from defects in the local environment (Hartschuh et al., 2003).

9, e) Thermal ablation: MWCNTs are more useful than SWCNTs for thermal treatment of cancer (Hirsch et al., 2003), because, the MWCNTs release substantial vibrational energy after exposure to near infrared light. The released energy within a tissue produces localized heating, which is responsible for destruction of cancer cells. Because MWCNTs have more available electrons per particle and also contain more metallic tubes than SWCNTs, they tend to absorb near infrared radiation at a faster rate.

9, f) CNT functionalization techniques:

Commercially available CNTs are highly contaminated with metal catalysts and amorphous carbons. That is why they are generally insoluble and not biocompatible. In order to make these materials less toxic and more biocompatible, a number of methods have been designed to attach appropriate molecules to the CNT surface, known as functionalization (Prato et al., 2008). It has been reported that intravenously injected functionalized CNTs are excreted via the biliary pathway without causing any significant harm (Liu et al., 2009). Generally CNTs can be either covalently or noncovalently functionalized with different chemical groups (Rosca et al., 2005). In terms of reactivity of CNTs with functional groups, CNTs are divided into two zones, i.e., the tips and the side walls. It has been found that CNT tips have a higher affinity for binding functional groups than do the side walls (Prato et al., 2008).

10. Exosomes: Therapeutic drug carriers and delivery vehicles. Exosomes are biological, vesicular nanostructures that propagate information and bioactivity within and between cells. By definition exosomes are biomolecular nanostructures released from cells, which carry specific biomolecular information as exosomal cargo. Most living cells release an array of extracellular vesicles (EVs), i.e., membrane liposomes which are 20–200 nm in size. The nomenclature of the different vesicle types depends on their cell of origin, as well as their function and size. Cells deliver microRNA (miRNA), messenger RNA (mRNA), proteins, and other biomolecules between intracellular organelles by membranevesicles, which contain receptors to ensure traffic specificity. These membrane vesicles are actively secreted by most cells and present in most body fluids, including blood, saliva, breast milk and sperm. There are three main types of such membrane vesicles: microparticles, microvesicles (100–1,000 nm), and exosomes (20–200 nm) (Sun et al., 2010; Lawson et al., 2016). Exosomes are bilayer membrane vesicles released by almost every mammalian cell type for intercellular communication and are unique to the cell of origin. For example, exosomes released from cancer cells are responsible for developing metastasis through such intercellular trafficking. Hence, exosomes are used in theranostic applications, because they display biomarker profiles specific to the diseased cell from which they are derived. Rose Johnstone coined the term “exosomes” (Johnstone et al., 1987, 2005). The Nobel Prize was awarded in 2013 to Ames E. Rothman, Randy W. Schekman and Thomas C. Südhof for their discoveries of a system regulating vesicle traffic, a major transport system in our cells (The Nobel Prize….2013).

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Cells produce and export molecular products, such as insulin into the bloodstream (Zheng et al., 2014). These molecules are presented to a “cell packaging service,” i.e., the exosomes, which are first released intracellularly. Initially, multivesicular endosomes (MVEs) are formed, surrounding the exosomes. These intracellular exosomes are incorporated into the MVEs in the cytoplasm. Abels and Breakefield (2016) described several mechanisms for generation and release of exosomes. The MVEs fuse with the cell membrane releasing the exosomes to the extracellular matrix (Vlassov et al., 2012). Rab GTPases (peripheral membrane proteins) have been found to facilitate this fusion of MVEs with the plasma membrane, including RAB11 and RAB35 (Savina et al., 2003; Hsu et al., 2010), which in turn release exosomes enriched with flotillin and other cell-specific proteins. 10, a) Isolation and characterization of exosomes: Exosomes are present in most human biological fluids, including blood, urine, saliva and breast milk. It needs careful isolation and purification from surrounding biological fluids for the use of exosomes as a biomarker source. A number of exosome purification techniques have been developed with adaptation to the biological fluid from which the vesicles are derived. The storage condition of human breast milk is an important factor for the final exosome concentration and integrity (Zonneveld et al., 2014). The most widely used isolation method is differential centrifugation, which means, selective removal of extracellular debris (Théry et al., 2006). But this method produces low yields of exosomes with excess protein. Another common method is solution sedimentation and low-speed centrifugation, inducing the precipitation of exosomes (van der Pol et al., 2014). Sucrose gradients are commonly employed to take advantage of the buoyant density in viscous fluids and to facilitate the isolation process (Oosthuyzen et al., 2013). All these isolation methods are time-consuming and often expensive. Specifically, for breast milk-derived exosomes, isolation and purification techniques optimized for high yields at minimal time and low cost are still lacking. The biophysical characterization of exosomes is made by determination of their size and concentration (Lane et al., 2015). Measurements by dynamic light scattering (DLS) have been reported in literatures. DLS determines the hydrodynamic radius and may not separate different populations (e.g., 100 and 200 nm), which can compromise the final value for mean size. The Nanosight technique is based on nanoparticle tracking analysis (NTA) for both size and concentration determination. This method measures the hydrodynamic radius, too, and comes therefore with the same limitations as DLS. Exosomes have a homogenous “cup-shaped” morphology, as determined by negative-staining electron microscopy (Théry et al., 2002; Simons and Raposo, 2009). For visualization of exosomes, transmission electron microscopy (TEM) can be applied, but the low

density of exosomes is the limitation of the power of this technique. Furthermore, if the samples are not highly pure, it can be difficult to differentiate proteins, exosomes and other vesicles. Van der Pol et al. (2014) compared particle size distribution of urinary exosomes and microvesicles using TEM, flowcytometry, NTA and TRPS. They have found that each method gives a different concentration and particle size distribution. Taylor et al. (2011) reported on exosome isolation specifically optimized for proteomic analyses and RNA profiling. The exosomes isolated by different methods were analyzed in terms of quantity and quality of specific RNAs and marker proteins. ExoQuickTM precipitation of circulating exosomes produced RNA and protein with higher purity and quantity than chromatography, ultracentrifugation, and DynaBeads. While this precipitation method does not provide specificity of the originating cell, the high quantity and quality of exosomal proteins and RNA improve both sensitivity and accuracy of subsequent biomolecular characterization, such as miRNA profiling and mass spectrometric proteomics. Characterization of exosomal cargo is of great interest because this molecular content can inform on biogenesis, targeting, and cellular effects of exosomes and may be a source of biomarkers for disease diagnosis, prognosis and response to treatment (Schey et al., 2015). The cargo of exosomes is not a result of a random process, rather it involves a complex sorting mechanism that favors specific biomolecules over others (Abels and Breakefield, 2016; Stevanato et al., 2016). The contents of exosomes have been shown to change when transitioning from health to disease, including conditions like viral infections, neurodegeneration (Alzheimer’s, Huntington’s), and cancer. The majority of the literature on biomolecular profiling of exosomes reports on RNA and proteins. Nucleic acids were first described in exosomes released by mast cells (Valadi et al., 2007). While the mRNAs or miRNAs secreted within exosomes are not random, the exact export mechanism has not yet been experimentally confirmed (Batagov et al., 2011; Colombo et al., 2014). There is growing interest in using miRNAs as biomarkers for disease diagnosis. Encapsulation of miRNAs in exosomes and exosome-like particles confers protection and provides a pathway for intestinal and vascular endothelial transport by endocytosis, as well as delivery to peripheral tissues (Cui et al., 2017). 10, b) Exosomes deliver molecular cargo: Exosomes play many important roles in many biological processes, including: intercellular communication; immune function; development and differentiation of stem cells; neuronal function; cell signaling; tissue regeneration; and viral replication (Rashed et al., 2017). Exosomes have been isolated from a variety of cell types in vitro. They have the ability to transfer molecular cargo and to be selectively taken up by specific cells, thereby reprogramming the



target cell and, possibly, inducing diseases. On the other hand, they can also provide new avenues for treatment and diagnosis. The urgent need for clinical biomarkers accessible by minimally invasive means is encouraging further biomarker research. Yet, in cancer and other malignancies, translation of candidate markers into sensitive and robust assays is still limited. Exosomes could offer a new route to biomarker discovery, validation and application due to their cell origin-specific cargo and accessibility by minimally invasive sampling (Worst et al., 2017). Zhang et al. (2015) describe exosomes as “small particles, big players” as they are also good candidates for generating improved cancer therapies. Exosomes are involved in the complete cancer life cycle, including the initiation, growth, progression and drug resistance of tumors (Zhang et al., 2015; Kosaka et al., 2012). Compared to exosomes secreted from healthy cells, a larger amount of exosomes is released from cancer cells, which promotes transformation of local healthy epithelial cells into cancerous cells, subsequently invading the extracellular matrix and contributing to distal metastasis (Tickner et al., 2014). Hoshino et al. (2015) reported how tumor-derived exosomes create a favorable microenvironment at future metastatic sites and mediate nonrandom patterns of metastasis, because the protein content of the tumor determines to a large extent the organotropism. 10, c) Role of exosomes in breast milk: Exosomes have been studied extensively for their potential as a biomarker source and a delivery system for bioactives. The main application areas are disease diagnostics and drug delivery. The roles of exosomes in breast milk include the regulation of immune response and inflammation. More recently, it was found that they promote epithelial growth in the intestine (Hock et al., 2017). Breast milk significantly decreases the incidence of necrotising enterocolitis in infants. Yet, Hock et al. found rat milk exosomes to enhance epithelial cell proliferation and viability. Liao et al. (2017) describe how exosomes can survive harsh conditions, such as digestion, subsequent to which they are taken up by human intestinal cells. Exosomes provide a stable transportation mechanism for the transfer of miRNA under severe conditions. 10, d) Exosomes release viral microRNAs in HIV infection: Bernard et al. (2014) reported that HIV infection of primary alveolar macrophages produced elevated levels of viral microRNAs vmiR88, vmiR99 and vmiR-TAR in cell extracts and in exosome preparations from conditioned medium. Furthermore, these miRNAs were also detected in exosome fraction of sera from HIV-infected persons. Importantly, vmiR88 and vmiR99 (but not vmiR-TAR) stimulated human macrophage TNFa release, which is

dependent on macrophage TLR8 expression. These data support a potential role for HIV-derived vmiRNAs released from infected macrophages as contributing to chronic immune activation in HIV-infected persons, and may represent a novel therapeutic target to limit AIDS pathogenesis. 10, e) Exosome as a therapeutic delivery system: An exosome-based delivery system has particular benefits such as specificity, safety, and stability. By their homing characteristic, exosomes can deliver their cargo to specific targets over a long distance. Exosomes can also be used to deliver interfering RNA (siRNA) or pharmaceutically active substances (Aryani and Denecke, 2016). As exosomes are small and native to animals, they are able to avoid phagocytosis, fuse with the cell membrane, and bypass the engulfment by lysosomes. The fact that exosomes are a natural product of the body results in a low immune response (Ha et al., 2016). Exosome also can exhibit increased stability in the blood that allows them to travel long distances within the body under both physiological and pathological conditions. Furthermore, exosomes have a hydrophilic core, which makes them suitable to host water-soluble drugs (Jiang and Gao, 2017). Several methods for exosome loading have been suggested to date, which can be classified into two different strategies, cargo loading after isolation and cargo loading during formation (Van der Meel et al., 2014). For cargo loading after isolation, a few loading procedures have been reported. One of the methods is electroporation. By applying an electric field to a suspension of exosomes (or cells) and the therapeutic cargo of choice, pores are created into the lipid bilayer membrane, thereby facilitating the movement of cargo into the lumen of the exosomes. Simple incubation of exosomes with the cargo was also used as one of the methods of loading exosomes. Curcumin was efficiently loaded into exosomes after only 5 min of incubation at 22 °C and was shown to mediate significant anti-inflammatory effects in several disease models such as brain inflammation, autoimmune disease and brain tumors (Johnsen et al., 2014; Zhuang et al., 2011). Another method to load cargo into exosomes is sonication. A drug-exosome mixture was sonicated for six cycles of 30 s on/off for a total of 3 min with 2 min cooling period, which resulted in effective drug loading into exosomes. Taking the size, the zeta potential and the quantity of drug loading into account, there are no significant changes in the structure and content of exosomal membranes after sonication (Jiang and Gao, 2017). The extensive reformation and reshaping of exosomes upon sonication and extrusion procedures enabled catalase diffusion across the relatively tight and highly structured lipid bilayers and resulted in the high loading efficiency of exosomal carriers (20–26% loading capacity) (Batrakova and Kim, 2015).

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10, f) Modified exosome for drug delivery: Nowadays, nanoscale drug delivery systems have attained considerable importance. Various nano-based drug formulations have been used to improve the therapeutic efficacy of chemical and biomolecular drugs. Exosomes function as intercellular communication tools. They transfer their cargo to recipient cells (Luan et al., 2017). The ideal drug delivery system (DDS) should be capable of site-specific delivery of incorporated therapeutics, avoid recognition and premature degradation by the body’s immune defenses and controlled release of cargo molecules upon selective stimuli. Exosomes have the ability to deliver endogenous biological cargo, such as small RNAs, mRNAs, and proteins across cells. Exosomes have shown many advantages in terms of biocompatibility and reduced clearance rates in view of their natural origin in comparison with other DDS. Moreover, they show little long-term accumulation in any organ or tissue, with concurrent low systemic toxicity, and also facilitated cellular uptake (Goh et al., 2017). 10, g) Surface modified exosomes for cerebral ischemia therapy: Cerebral ischemia can be classified as the condition whereby impaired blood flow does not allow sufficient deliver of oxygen and glucose, leading to energy depletion, over-activation of glutamate receptors and release of excess glutamate, an increase of intracellular calcium, loss of membrane potential and cell depolarization, and eventually, cell death (Wang et al., 2018). Using exosomes as nanocarriers is one of many methods for cerebral ischemic therapy. The targeting ability of exosomes can be improved through appropriate surface modification. Tian et al. has proposed a simple, rapid and efficient method to conjugate functional ligands onto exosomal surfaces using bioorthogonal copper-free azide-alkyne cycloaddition. The cyclo(Arg-Gly-Asp-DTyr-Lys) peptide [c(RGDyK)], which exhibits high affinity to integrin αvβ3 in reactive cerebral vascular endothelial cells after ischemia specifically, was conjugated on the mesenchymal stromal cell (MSC)-derived exosome surface. Furthermore, curcumin, a natural polyphenol from Curcuma longa, was loaded onto the cRGD-Exo. The result shows that modified exosome molecules showed greater accumulation in ischemic brain as compared to unmodified exosome molecules (Tian et al., 2018). CONCLUSION In this review article we have tried to present application and importance of various types of nanomaterials and nanostructures in biology and medicine in the same platform such as Ag NPs, Au NPs, CuO NPs, ZnO NPs, TiO2 NPs, CdO NPs, CaO NPs, MgO NPs, Carbon nanotubes and exosomes. The antibacterial effects of Ag NPs have potential implications for human health. Gold

nanoparticles play unique roles in drug and gene delivery, targeting and imaging applications. Au NPs of various shapes can undergo a strong plasmon resonance with light which, have been considered for use in photothermal therapeutic programs directed at different types of target cells including cancers, bacteria and parasites. CuO NPs showed excellent antimicrobial activity against various bacterial strains (E. coli, P. aeruginosa, K. pneumonia, E. faecalis, S. flexneri, S. typhimurium, P. vulgaris, and S. aureus). Nontoxic antibacterial TiO2 NPs can be used in human food, drugs, cosmetics, and food contact materials. Cadmium nanoparticles i.e. quantum dots (QDs) have the potential for revolutionizing biological imaging at the cellular level, cancer detection, treatment, and targeted drug delivery. Synaphic delivery of chemotherapeutic agents is an important property of CaO NPs. MgO nanoflakes can be used as cancer drug carrier. In comparison to other metal oxide NPs, ZnO NPs are inexpensive and relatively less toxic because Zn++ is intrinsic to human body. They have many important biomedical applications such as antibacterial, anticancer, antioxidant, drug delivery, diabetes treatment, anti-inflammation, wound healing, and bioimaging. Carbon nanotubes a new kind of nanomaterials other than metal oxide NPs are tubular materials with nanometer-sized diameters and axial symmetry, having unique properties that can be used as cancer theranostics. CNTs have the potential to deliver drugs directly to targeted cells and tissues. Multi-walled CNTs are more useful than single-walled CNTs for thermal treatment of cancer. Exosomes are biological, cellular, vesicular nanostructures that transport biomolecular information as cargo. They are vesicular carriers for intercellular communication. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Exosomes, as therapeutic drug carriers and delivery vehicles across biological membranes are current research perspectives and future challenges. Hence, as a nanodelivery system they might be a key to the future of nanomedicine. This is an endeavor to present all this comparative information to the nano researchers in an orchestrated way.

REFERENCES

Abels ER, Breakefield XO. (2016). Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell. Mol. Neurobiol. 36: 301–312.

Adibkia K, Omidi Y, Siahi MR, Javadzadeh AR, Barzegar-Jalali M, Barar J, Maleki N, Mohammadi G, Nokhodchi A. (2007). Inhibition of endotoxin-induced uveitis by methylprednisolone acetate nanosuspension in rabbits. J. Ocul. Pharmacol. Ther. 23: 421-432.

Adibkia KH, Barzegar-Jalali M, Nokhodchi A, Siahi Shadbad MR, Omidi YA, Javadzadeh Y, Mohammadi GH. (2009). A review on the methods of preparation of pharmaceutical nanoparticles. Pharmaceutical. Sciences. 15 (4): 303-314.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Maleki%20N%5BAuthor%5D&cauthor=true&cauthor_uid=17900230

https://www.ncbi.nlm.nih.gov/pubmed/?term=Mohammadi%20G%5BAuthor%5D&cauthor=true&cauthor_uid=17900230

https://www.ncbi.nlm.nih.gov/pubmed/?term=Nokhodchi%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17900230

https://www.ncbi.nlm.nih.gov/pubmed/?term=Nokhodchi%20A%5BAuthor%5D&cauthor=true&cauthor_uid=17900230



Alivisatos P. (2004). The use of nanocrystals in biological detection. Nat. Biotechnol. 22: 47–52.

Altin T, S¨okmen M. (2014). Preparation of TiO2-polystyrene photocatalyst from waste material and its usability for removal of various pollutants. Applied. Catalysis. B: Environmental. 144: 694–701.

Arakha M, Roy J, Nayak PS, Mallick B, Jha, S. (2017). Zinc oxide nanoparticle energy band gap reduction triggers the oxidative stress resulting into autophagy-mediated apoptotic cell death. Free. Radic. Biol. Med. 110: 42–53.

Arora B, Murar M, Dhumale V. (2015). Antimicrobial potential of TiO2 nanoparticles against MDR Pseudomonas aeruginosa. J. Experimental. Nanoscience. 10(11): 819-827.

Arsawang U, Saengsawang O, Rungrotmongkol T, Sornmee P, Wittayanarakul K, Remsungnen T, Hannongbua S. (2011). How do carbon nanotubes serve as carriers for gemcitabine transport in a drug delivery system? J. Mol. Graph. Model. 29: 591–596.

Aryani A, Denecke B. (2016). Exosomes as a nanodelivery system: a key to the future of neuromedicine? Mol. Neurobiol. 53: 818–834.

Azam A, Ahmed AS, Oves M, Khan MS, Habib SS, Memic A. (2012). Antimicrobial activity of metal oxide nanoparticles against Gram-positive and Gram-negative bacteria: a comparative study. Int. J. Nanomedicine. 7: 6003-6009.

Bae DH, Yeon JH, Park SY, Lee DH, Ha SD. (2006). Bactericidal Effect of CaO (Scallop- Shell powder) on Foodborne Pathogenic Bacteria. Arch. Pharm. Res. 29: 298-301.

Bahrami K, Nazari P, Nabavi M, Golkar M, Almasirad A, Shahverdi AR. (2014). Hydroxyl capped silver-gold alloy nanoparticles: characterization and their combination effect with different antibiotics against Staphylococcus aureus. Nanomed. J. 1: 155-161.

Bai DP, Zhang XF, Zhang GL, Huang YF, Gurunathan S. (2017). Zinc oxide nanoparticles induce apoptosis and autophagy in human ovarian cancer cells. Int. J. Nanomedicine. 12: 6521–6535.

Batagov AO, Kuznetsov VA, Kurochkin IV. (2011). Identification of nucleotide patterns enriched in secreted RNAs as putative cis-acting elements targeting them to exosome nano-vesicles. BMC. Genomics. 12: S18.

Batra R, Davies JN, Wheatley D. (2009). Extensive arterial and venous thrombo-embolism with chemotherapy for testicular cancer: A case report. Cases. J. 2: 9082.

Batrakova EV, Kim MS. (2015). Using exosomes, naturally-equipped nanocarriers, for drug delivery. J. Control. Release. 219: 396-405.

Beg S, Rizwan M, Sheikh AM, Hasnain MS, Anwer K, Kohli K. (2011). Advancement in carbon nanotubes: Basics, biomedical applications and toxicity. J. Pharm. Pharmacol. 63: 141–163.

Bekyarova E, Ni Y, Malarkey EB, Montana V, McWilliams JL, Haddon RC, Parpura, V. (2005). Applications of carbon nanotubes in biotechnology and biomedicine. J. Biomed. Nanotechnol. 1: 3–17.

Bernard MA, Zhao H, Yue SC, Anandaiah A, Koziel H, Tachado SD. (2014). Novel HIV-1 MiRNAs Stimulate TNFa Release in Human Macrophages via TLR8 Signaling Pathway. PLOS ONE www.plosone.org 9.

Besinis A, De Peralta T, Handy RD. (2014). The antibacterial effects of silver, titanium dioxide and silica dioxide nanoparticles compared to the dental disinfectant chlorhexidine on Streptococcus mutans using a suite of bioassays. Nanotoxicol. 8: 1-16.

Bhattacharya R, Patra CR, Earl A, Wang S, Katarya A, Lu L, Kizhakkedathu JN, Yaszemski MJ, Greipp PR, Mukhopadhyay D, Mukherjee P. (2007). Attaching folic acid on gold nanoparticles using noncovalent interaction via different polyethylene glycol backbones and targeting of cancer cells. Nanomedicine. 3: 224–238.

Boguniewicz M, Leung DY. (2011). Atopic dermatitis: a disease of altered skin barrier and immune dysregulation. Immunol. Reviews. 242(1): 233–246.

Bonetta S, Bonetta S, Motta F, Strini A, Carraro E. (2013). Photocatalytic bacterial inactivation by TiO2-coated surfaces. AMB. Express. 3(1): 1–8.

Bonoiu AC, Mahajan SD, Ding H, Roy I, Yong KT, Kumar R, Hu R, Bergey EJ, Schwartz SA, Prasad PN. (2009). Nanotechnology approach for drug addiction therapy: gene silencing using delivery of gold nanorod–siRNA nanoplex in dopaminergic neurons. P.N.A.S. 106(14): 5546–5550.

Boyer C, Priyanto P, Davis TP, Pissuwan D, Bulmus V, Kavallaris M, Teoh WY, Amal R, Carroll M, Woodward R, Pierree TS. (2010). Anti-fouling magnetic nanoparticles for siRNA delivery. J. Mat. Chem. 20: 255-265.

Burygin GL, Khlebtsov BN, Shantrokha AN, Dykman LA, Bogatyrev VA, Khlebtsov NG. (2009). On the enhanced antibacteria activity of antibiotics mixed with gold nanoparticles. Nanoscale. Res. Lett. 4: 794–801.

Butt AR, Ejaz S, Baron JC, Ikram M, Ali S. (2015). CaO nanoparticles as a potential drug delivery agent for biomedical applications. Digest. J. Nanomaterials. Biostructures. 10: 799– 809.

Buzea C, Pacheco Ii, Robbie K. (2007). Nanomaterials and nanoparticles: sources and toxicity. Biointerphases. 2: MR17-71.

Castellano JJ, Shafii SM, Ko F, Donate G, Wright TE, Mannari RJ, Payne WG, Smith D J, Robson MC. (2007). Comparative evaluation of silver-containing antimicrobial dressings and drugs. Int. Wound. J. 4: 14–22.

Cataldo F, Da Ros T. (2008). Medicinal chemistry and pharmacological potential of fullerenes and carbon nanotubes. Trieste: Springer. Editors: Cataldo Franco, da Ros Tatiana (Eds.).

Chandrasekaran M, Pandurangan M. (2016). In vitro selective anti-proliferative effect of zinc oxide nanoparticles against co-cultured C2C12 myoblastoma cancer and 3T3-L1 normal cells. Biol. Trace. Element. Res. 172(1): 148–154.

Chang TM, Prakash S. (2001). Procedures for microencapsulation of enzymes, cells and genetically

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sornmee%20P%5BAuthor%5D&cauthor=true&cauthor_uid=21167762

https://www.ncbi.nlm.nih.gov/pubmed/?term=Wittayanarakul%20K%5BAuthor%5D&cauthor=true&cauthor_uid=21167762

https://www.ncbi.nlm.nih.gov/pubmed/?term=Remsungnen%20T%5BAuthor%5D&cauthor=true&cauthor_uid=21167762

https://www.ncbi.nlm.nih.gov/pubmed/?term=Lee%20DH%5BAuthor%5D&cauthor=true&cauthor_uid=16681035

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ha%20SD%5BAuthor%5D&cauthor=true&cauthor_uid=16681035


https://www.ncbi.nlm.nih.gov/pubmed/?term=Kim%20MS%5BAuthor%5D&cauthor=true&cauthor_uid=26241750

https://www.ncbi.nlm.nih.gov/pubmed/26241750


https://www.ncbi.nlm.nih.gov/pubmed/?term=Montana%20V%5BAuthor%5D&cauthor=true&cauthor_uid=19763242

https://www.ncbi.nlm.nih.gov/pubmed/?term=McWilliams%20JL%5BAuthor%5D&cauthor=true&cauthor_uid=19763242

https://www.ncbi.nlm.nih.gov/pubmed/?term=McWilliams%20JL%5BAuthor%5D&cauthor=true&cauthor_uid=19763242

https://www.ncbi.nlm.nih.gov/pubmed/?term=Haddon%20RC%5BAuthor%5D&cauthor=true&cauthor_uid=19763242

https://www.ncbi.nlm.nih.gov/pubmed/?term=Parpura%20V%5BAuthor%5D&cauthor=true&cauthor_uid=19763242

http://www.plosone.org/

https://www.ncbi.nlm.nih.gov/pubmed/?term=Payne%20WG%5BAuthor%5D&cauthor=true&cauthor_uid=17651227

https://www.ncbi.nlm.nih.gov/pubmed/?term=Smith%20DJ%5BAuthor%5D&cauthor=true&cauthor_uid=17651227

https://www.ncbi.nlm.nih.gov/pubmed/?term=Robson%20MC%5BAuthor%5D&cauthor=true&cauthor_uid=17651227


Saha and Bal 34

engineered microorganisms. Mol. Biotechnol. 17: 249–260.

Chatterjee AK, Chakraborty R, Basu T. (2014). Mechanism of antibacterial activity of copper nanoparticles. Nanotechnol. 25: 135101.

Chatterjee T, Chakraborti S, Joshi P, Singh SP, Gupta V, Chakrabarti P. (2010). The effect of zinc oxide nanoparticles on the structure of the periplasmic domain of the Vibrio cholerae ToxR protein. FEBS. J. 277(20): 4184–4194.

Chawengkijwanich C, Hayata Y. (2008). Development of TiO2 powder-coated food packaging film and its ability to inactivate Escherichia coli in vitro and in actual tests. Int. J. Food. Microbiol. 123(3): 288–292.

Check E. (2002). Gene therapy: a tragic setback. Nature. 420(6912): 116–118.

Chen CC, Lin YP, Wang CW, Tzeng HC, Wu CH, Chen YC, Chen CP, Chen LC, Wu YC. (2006). DNA-gold nanorod conjugates for remote control of localized gene expression by near infrared irradiation. J. Am. Chem. Soc. 128: 3709–3715.

Chen PC, Mwakwari SC, Oyelere AK. (2008). Gold nanoparticles: from nanomedicine to nanosensing. Nanotech. Sci. Appl. 1: 45–66.

Chen Q, Xue Y, Sun J. (2013). Kupfer cell-mediated hepatic injury induced by silica nanoparticles in vitro and in vivo. Int. J. Nanomedicine. 8: 1129-1140.

Chen Y-H, Tsai C-Y, Huang P-Y, Chang M-Y, Cheng P-C, Chou C-H, Chen D-H, Wang C-R, Shiau A-L, Wu C-L. (2007). Methotrexate conjugated to gold nanoparticles inhibits tumor growth in a syngeneic lung tumor model. Mol. Pharm. 4: 713–722.

Cheng Y, Anna CS, Meyers JD, Panagopoulos I, Fei B, Burda C. (2008). Highly efficient drug delivery with gold nanoparticle vectors for in vivo photodynamic therapy of cancer. J. Am. Chem. Soc. 130: 10643–10647.

Choi S-W, Kim W-S, Kim J-H. (2003). Surface modification of functional nanoparticles for controlled drug delivery. J. Dispers. Sci. Technol. 24: 475–487.

Colombo M, Raposo G, Théry C. (2014). Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell. Dev. Biol. 30: 255–289.

Crystal RG. (1995). Transfer of genes to humans: early lessons and obstacles to success. Science. 270(5235): 404–410.

Cui J, Zhou B, Ross SA, Zempleni J. (2017). Nutrition, microRNAs, and human health. Adv. Nutr. Int. Rev. J. 8: 105–112.

Cui Y, Zhao Y, Tian Y, Zhang W, Lü X, Jiang X. (2012). The molecular mechanism of action of bactericidal gold nanoparticles on Escherichia coli. Biomaterials. 33: 2327-2333.

Dakrong P, Takuro N, Michael B. (2011). The forthcoming applications of gold nanoparticles in drug and gene delivery systems. J. Control. Rel. 149: 65-71.

Danailov D, Keblinski P, Nayak S, Ajayan PM. (2002). Bending properties of carbon nanotubes encapsulating solid nanowires. J. Nanosci. Nanotechnol. 2: 503–507.

Daniel M-C, Astruc D. (2003). Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. Chem. Rev. 104: 293–346.

De Souza A, Mehta D, Leavitt RW. (2006). Bactericidal activity of combinations of silver–water dispersion with 19 antibiotics against seven microbial strains. Curr. Sci. 91: 926–929.

Deng Y, Zhang H. (2013). The synergistic effect and mechanism of doxorubicin-ZnO nanocomplexes as a multimodal agent integrating diverse anticancer therapeutics. Int. J. Nanomedicine. 8: 1835–1841.

Dhar S, Liu Z, Thomale J, Dai H, Lippard SJ. (2008). Targeted single-wall carbon nanotube-mediated Pt(IV) prodrug delivery using folate as a homing device. J. Am. Chem. Soc. 130: 11467–11476.

Divya M, Vaseeharan B, Abinaya M, Vijayakumar S, Govindarajan M, Alharbi NS, Kadaikunnan S, Khaled JM, Benelli G. (2018). Biopolymer gelatin-coated zinc oxide nanoparticles showed high antibacterial, antibiofilm and anti-angiogenic activity. J. Photochem. Photobiol. B. 178: 211–218.

Duran N, Marcarto PD, De Souza GIH, Alves OL, Esposito E. (2007). Antibacterial effect of silver nanoparticles produced by fungal process on textile fabrics and their effluent treatment. J. Biomed. Nanotechnol. 3: 203–208.

Dutta RK, Nenavathu BP, Gangishetty MK, Reddy AV. (2013). Antibacterial effect of chronic exposure of low concentration ZnO nanoparticles on E. coli. J. Environ. Sc. Health: Part A. 48(8): 871–878.

Ebbesen TW, Ajayan PM. (1992). Large-scale synthesis of carbon nanotubes. Nature. 358: 220–222.

Emami-Karvani Z, Chehrazi P. (2011). Antibacterial activity of ZnO nanoparticle on gram-positive and gram-negative bacteria. Afr. J. Microbiol. Res. 5: 1368-1373.

Erathodiyil N, Ying JY. (2011). Functionalization of inorganic nanoparticles for bioimaging applications. Account. Chem. Res. 44(10): 925–935.

Feazell RP, Nakayama-Ratchford N, Dai H, Lippard SJ. (2007). Soluble Single-Walled Carbon Nanotubes as Longboat Delivery Systems for Platinum(IV) Anticancer Drug Design. J. Am. Chem. Soc. 129(27): 8438–8439.

Felnerova D, Viret J-F, Reinhard G-k, Moser C. (2004). Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs. Curr. Opin. Biotechnol. 15: 518–529.

Feng QL, Wu J, Chen GQ, Cui FZ, Kim TN, Kim JO. (2000). Mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus. J. Biomed. Mater. Res. 52: 662-668.

Fen-Ying K, Jin-Wei Z, Rong-Fang L, Zhong-Xia W, Wen-Juan W, Wei W. (2017). Unique Roles of Gold Nanoparticles in Drug Delivery, Targeting and Imaging Applications. Molecules. 22: 1445-1458.

Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE. (2006). Chronic inflammation: importance of NOD2 and

https://www.ncbi.nlm.nih.gov/pubmed/?term=Vijayakumar%20S%5BAuthor%5D&cauthor=true&cauthor_uid=29156349

https://www.ncbi.nlm.nih.gov/pubmed/?term=Vijayakumar%20S%5BAuthor%5D&cauthor=true&cauthor_uid=29156349

https://www.ncbi.nlm.nih.gov/pubmed/?term=Govindarajan%20M%5BAuthor%5D&cauthor=true&cauthor_uid=29156349

https://www.ncbi.nlm.nih.gov/pubmed/?term=Alharbi%20NS%5BAuthor%5D&cauthor=true&cauthor_uid=29156349

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kadaikunnan%20S%5BAuthor%5D&cauthor=true&cauthor_uid=29156349

https://www.ncbi.nlm.nih.gov/pubmed/?term=Khaled%20JM%5BAuthor%5D&cauthor=true&cauthor_uid=29156349


https://www.ncbi.nlm.nih.gov/pubmed/?term=Benelli%20G%5BAuthor%5D&cauthor=true&cauthor_uid=29156349



NALP3 in interleukin-1 beta generation. Clin. Experim. Immunol. 147(2): 227–235.

Gao L, Nie L, Wang T, Qin Y, Guo Z, Yang D, Yan, X. (2006). Carbon nanotube delivery of the GFP gene into mammalian cells. Chem. BioChem. 7(2): 239–242.

Gedda G, Pandey S, Lina Yu-C, Wu H-F. (2015). Antibacterial effect of calcium oxide nano-plates fabricated from shrimp shells. Green. Chem. Issue 6.

Geller RJ, Chevalier RL, Spyker DA. (1986). Acute amoxicillin nephrotoxicity following an overdose. Clin. Toxicol. 24: 175–182.

Ghaffari SB, Sarrafzadeh MH, Fakhroueian Z, Shahriari S, Khorramizadeh MR. (2017). Functionalization of ZnO nanoparticles by 3-mercaptopropionic acid for aqueous curcumin delivery: synthesis, characterization, and anticancer assessment. Materials. Sc. Engin. C. 79: 465–472.

Ghanbari H, de Mel A, Seifalian AM. (2011). Cardiovascular application of polyhedral oligomeric silsesquioxane nanomaterials: A glimpse into prospective horizons. Int. J. Nanomedicine. 6: 775–786.

Ghosh P, Han G, De M, Kim CK, Rotello VM. (2008). Gold nanoparticles in delivery applications. Adv. Drug. Deliv. Rev. 60: 1307–1315.

Gibson JD, Khanal BP, Zubarev ER. (2007). Paclitaxel-functionalized gold nanoparticles. J. Am. Chem. Soc. 129: 11653–11661.

Godymchuk A, Frolov G, Gusev A, Zakharova O, Yunda EN, Kuznetsov D, Kolesnikov E. (2015). Antibacterial Properties of Copper Nanoparticle Dispersions: Influence of Synthesis Conditions and Physicochemical Characteristics. In IOP Conference Series: Materials Science and Engineering (1 ed., Vol. 98). [012033] Institute of Physics Publishing. https://doi.org/10. 1088/1757-899X/98/1/012033

Goh WJ, Zou S, Ong WY, Torta F, Alexandra AF, Schiffelers RM, Storm G, Wang JW, Czarny B, Pastorin G. (2017). Bioinspired cell-derived nanovesicles versus exosomes as drug delivery systems: a cost-effective alternative. Sci. Rep. 7: 14322.

Gokulakrishnan R, Ravikumar S, Raj JA. (2012). In vitro antibacterial potential of metal oxide nanoparticles against antibiotic resistant bacterial pathogens. Asian. Pac. J. Trop. Dis. 2(5): 411-413.

Grass G, Rensing C, Solioz M. (2011). Metallic copper as an antimicrobial surface. Appl. Environ. Microbiol. 77: 1541-1547.

Gu H, Ho PL, Tong L, Wang L, Xu B. (2003). Presenting vancomycin on nanoparticles to enhance antimicrobial activities. Nano. Lett. 3: 1261–1263.

Gu Y-J, Cheng J, Lin C-C, Lam YW, Cheng SH, Wong W-T. (2009). Nuclear penetration of surface functionalized gold nanoparticles. Toxicol. Appl. Pharmacol. 237: 196–204.

Gumiero M, Peressini D, Pizzariello A, Sensidoni A, Iacumin L, Comi G, Toniolo, R. (2013). Effect of TiO2 photocatalytic activity in a HDPE-based food packaging

on the structural and microbiological stability of a short-ripened cheese. Food. Chem. 138(2-3): 1633–1640.

Guo CY, Sun L, Chen XP, Zhang DS. (2013). Oxidative stress, mitochondrial damage and neuro degenerative diseases. Neural. Regeneration. Res. 8(21): 2003–2014.

Gupta P, Vermani K, Garg S. (2002). Hydrogels: from controlled release to pH-responsive drug delivery. Drug. Discov. Today. 7: 569–579.

Gupta K, Singh RP, Pandey A, Pandey A. (2013). Photocatalytic antibacterial performance of TiO2 and Ag-doped TiO2 against S. aureus, P. aeruginosa. Beilsten. J. Nanotechnol. 4(1): 345–351.

Gurunathan S, Han JW, Dayem AA, Eppakayala V, Kim JH. (2012). Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa. Int. J. Nanomedicine. 7: 5901-5914.

Gyawali R, Ibrahim SA, Abu Hasfa SH, Smqadri SQ, Haik Y. (2011). Antimicrobial activity of copper alone and in combination with lactic acid against Escherichia coli O157: H7 in laboratory medium and on the surface of lettuce and tomatoes. J. Pathog. 2011: 650968.

Ha D, Yang N, Nadithe V. (2016). Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta. Pharm. Sin. B. 6: 287–296.

Haghi M, Hekmatafshar M, Janipour MB, gholizadeh SS, Faraz Mk, Sayyadifar F, Ghaedi, M. (2012). Antibacterial effect of TiO2 nanoparticles on pathogenic strain of E. coli. Int. J. Adv. Biotechnol. Res. 3(3): 621-624.

Hajipour MJ, Fromm KM, Ashkarran AA, Jimenez De Aberasturi D, De Larramendi IR, Rojo T, Serpooshan V, Parak WJ, Mahmoudi M. (2012). Antibacterial properties of nanoparticles. Trends. Biotechnol. 30: 499-511.

Han G, Chari NS, Verma A, Hong R, Martin CT, Rotello VM. (2005). Controlled recovery of the transcription of nanoparticle-bound DNA by intracellular concentrations of glutathione. Bioconj. Chem. 16(6): 1356–1359.

Han G, Martin CT, Rotello VM. (2006). Stability of gold nanoparticle-bound DNA toward biological, physical, and chemical agents. Chem. Biol. Drug. Des. 67(1): 78–82.

Hans M, Erbe A, Mathews S, Chen Y, Solioz M, Mücklich, F. (2013). Role of copper oxides in contact killing of bacteria. Langmuir. 29: 16160-16166.

Hardman R. (2006). A toxicologic review of quantum dots: Toxicity depends on physicochemical and environmental factors. Environ. Health. Perspect. 114: 165–172.

Hariharan R, Senthilkumar S, Suganthi A, Rajarajan M. (2012). Synthesis and characterization of doxorubicin modified ZnO/PEG nanomaterials and its photodynamic action. J. Photochem. Photobiol. B: Biology. 116: 56–65.

https://doi.org/10.1088/1757-899X/98/1/012033

https://doi.org/10.1088/1757-899X/98/1/012033

https://www.ncbi.nlm.nih.gov/pubmed/?term=Goh%20WJ%5BAuthor%5D&cauthor=true&cauthor_uid=29085024

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ong%20WY%5BAuthor%5D&cauthor=true&cauthor_uid=29085024

https://www.ncbi.nlm.nih.gov/pubmed/?term=Storm%20G%5BAuthor%5D&cauthor=true&cauthor_uid=29085024

https://www.ncbi.nlm.nih.gov/pubmed/?term=Wang%20JW%5BAuthor%5D&cauthor=true&cauthor_uid=29085024

https://www.ncbi.nlm.nih.gov/pubmed/?term=Czarny%20B%5BAuthor%5D&cauthor=true&cauthor_uid=29085024

https://www.ncbi.nlm.nih.gov/pubmed/?term=Pastorin%20G%5BAuthor%5D&cauthor=true&cauthor_uid=29085024

https://www.ncbi.nlm.nih.gov/pubmed/?term=Pastorin%20G%5BAuthor%5D&cauthor=true&cauthor_uid=29085024

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sensidoni%20A%5BAuthor%5D&cauthor=true&cauthor_uid=23411292

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sensidoni%20A%5BAuthor%5D&cauthor=true&cauthor_uid=23411292

https://www.ncbi.nlm.nih.gov/pubmed/?term=Iacumin%20L%5BAuthor%5D&cauthor=true&cauthor_uid=23411292

https://www.ncbi.nlm.nih.gov/pubmed/?term=Comi%20G%5BAuthor%5D&cauthor=true&cauthor_uid=23411292

https://www.ncbi.nlm.nih.gov/pubmed/?term=Toniolo%20R%5BAuthor%5D&cauthor=true&cauthor_uid=23411292

https://www.ncbi.nlm.nih.gov/pubmed/?term=Serpooshan%20V%5BAuthor%5D&cauthor=true&cauthor_uid=22884769

https://www.ncbi.nlm.nih.gov/pubmed/?term=Serpooshan%20V%5BAuthor%5D&cauthor=true&cauthor_uid=22884769

https://www.ncbi.nlm.nih.gov/pubmed/?term=Parak%20WJ%5BAuthor%5D&cauthor=true&cauthor_uid=22884769

https://www.ncbi.nlm.nih.gov/pubmed/?term=Mahmoudi%20M%5BAuthor%5D&cauthor=true&cauthor_uid=22884769

https://www.ncbi.nlm.nih.gov/pubmed/?term=M%C3%BCcklich%20F%5BAuthor%5D&cauthor=true&cauthor_uid=24344971

https://www.ncbi.nlm.nih.gov/pubmed/?term=M%C3%BCcklich%20F%5BAuthor%5D&cauthor=true&cauthor_uid=24344971


Saha and Bal 36

Harris N, Ford MJ, Cortie MB. (2006). Optimization of

plasmonic heating by gold nanospheres and nanoshells. J. Phys. Chem. B. 110: 10701–10707.

Hartschuh A, Pedrosa HN, Novotny L, Krauss TD. (2003). Simultaneous fluorescence and Raman scattering from single carbon nanotubes. Science. 301: 1354–1356.

Hasselgren G, Olsson B, Cvek M. (1988). Effects of calcium hydroxide and sodium hypochlorite on the dissolution of necrotic porcine muscle tissue. J. Endodontics. 14: 125.

Hatamie A, Khan A, Golabi M, Turner AP, Beni V, Mak WC, Sadollahkhani, A.; Alnoor, H.; Zargar, B.; Bano, S.; Nur, O.; Willander, M. (2015). Zinc oxide nanostructure-modified textile and its application to biosensing, photocatalysis, and as antibacterial material. Langmuir. 31(39): 10913–10921.

Healey KR, Zhao Y, Perez WB, Lockhart SR, Sobel JD, Farmakiotis D, Kontoyiannis D P, Sanglard D, Taj-Aldeen SJ, Alexander BD. (2016). Prevalent mutator genotype identified in fungal pathogen Candida glabrata promotes multi-drug resistance. Nat. Commun. 7: 11128.

Hirsch LR, Stafford RJ, Bankson JA, Sershen SR, Rivera B, Price RE, Hazle JD, Halas N J, West JL. (2003). Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc. Natl. Acad. Sci. U S A. 100: 13549–13554.

Hock A, Miyake H, Li B, Lee C, Ermini L, Koike Y, et al. (2017). Breast milk derived exosomes promote intestinal epithelial cell growth. J. Pediatr. Surg. 52: 755–759.

Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, et al. (2015). Tumor exosome integrins determine organotropic metastasis. Nature. 527: 329–335.

Hsu C, Morohashi Y, Yoshimura S, Manrique-Hoyos N, Jung S, Lauterbach MA, Bakhti M, Grønborg M, Möbius W, Rhee J, et al. (2010). Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C. J. Cell. Biol. 189: 223–232.

Hsueh YH, Ke WJ, Hsieh CT, Lin KS, Tzou DY, Chiang CL. (2015). ZnO nanoparticles affect Bacillus subtilis cell growth and biofilm formation. PLoS. One. 10(6): Article ID e0128457.

Hu M, Chen J, Li ZY, Au L, Hartland GV, Li X, Marquez M, Xia Y. (2006). Gold nanostructures: engineering their plasmonic properties for biomedical applications. Chem. Soc. Rev. 35(11): 1084-1094.

Huang X, Jain PK, El-Sayed IH, El-Sayed MA. (2008). Plasmonic photothermal therapy (PPTT) using gold nanoparticles Laser. Med. Sci. 23: 217–228.

Hussein J, El-Banna M, Razik TA, El-Naggar ME. (2018). Biocompatible zinc oxide nanocrystals stabilized via hydroxyethyl cellulose for mitigation of diabetic complications. Int. J. Biol. Macromol. 107: 748–754.

Ilves M, Palomaki J, Vippola M, Lehto M, Savolainen K, Savinko T, Alenius, H. (2014). Topically applied ZnO

nanoparticles suppress allergen induced skin inflammation but induce vigorous IgE production in the atopic dermatitis mouse model. Part. Fibre. Toxicol. 11(1): 38.

Ipe BI, Mahima S, Thomas KG. (2003). Light-induced modulation of self-assembly on spiropyran-capped gold nanoparticles: a potential system for the controlled release of amino acid derivatives. J. Am. Chem. Soc. 125: 7174–7175.

Iswarya A, Vaseeharan B, Anjugam M. (2017). Multipurpose efficacy of ZnO nanoparticles coated by the crustacean immune molecule beta-1,3-glucan binding protein: toxicity on HepG2 liver cancer cells and bacterial pathogens. Colloids and Surfaces. B: Biointerfaces. 158: 257–269.

Ishwarya R, Vaseeharan B, Kalyani S, Banumathi B, Govindarajan M, Alharbi NS, Kadaikunnan S, Al-Anbr MN, Khaled JM, Benelli G. (2018). Facile green synthesis of zinc oxide nanoparticles using Ulva lactuca seaweed extract and evaluation of their photocatalytic, antibiofilm and insecticidal activity. J. Photochem. Photobiol. B. 178: 249–258.

Jamieson T, Bakhshi R, Petrova D, Pocock R, Imani M,

Seifalian AM. (2007). Biological applications of quantum dots. Biomaterials. 28: 4717–4732.

Jiang XC, Gao JQ. (2017). Exosomes as novel bio-carriers for gene and drug delivery. Int. J. Pharm. 521: 167–175.

Jiang Y, Zhang L, Wen D, Ding Y. (2016). Role of physical and chemical interactions in the antibacterial behavior of ZnO nanoparticles against E. coli. Materials. Sc. Eng.: C. 69: 1361–1366.

Jin T, He Y. (2011). Antibacterial activities of magnesium oxide (MgO) nanoparticles against foodborne pathogens. J. Nanoparticle. Res. 13: 6877–6885.

Jones N, Ray B, Ranjit KT, Manna AC. (2008). Antibacterial activity of ZnO nanoparticle suspensions on a broad spectrum of microorganisms. FEMS. Microbiol. Lett. 279: 71–76.

Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M. (2014). A comprehensive overview of exosomes as drug delivery vehicles — Endogenous nanocarriers for targeted cancer therapy. Biochimica. et Biophysica. Acta. (BBA). 1846(1): 75-87.

Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. (1987). Vesicle formation during reticulocyte maturation. Association of plasmamembrane activities with released vesicles (exosomes). J. Biol. Chem. 262: 9412–9420.

Johnstone RM. (2005). Revisiting the road to the discovery of exosomes. BloodCells. Mol. Dis. 34: 214–219.

Juzenas P, Chen W, Sun YP, Coelho MAN, Genralov R, Genralova N, Christensen IL. (2008) Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer. Adv. Drug. Delivery. Revs. 60: 1600–1614.

Kang S, Pinault M, Pfefferle LD, Elimelech M. (2007). Single-walled carbon nanotubes exhibit strong antimicrobial activity. Langmuir. 23: 8670-8673.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Turner%20AP%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Beni%20V%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Mak%20WC%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Mak%20WC%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sadollahkhani%20A%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Alnoor%20H%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zargar%20B%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bano%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bano%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Nur%20O%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Willander%20M%5BAuthor%5D&cauthor=true&cauthor_uid=26372851

https://www.ncbi.nlm.nih.gov/pubmed/?term=Healey%20KR%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zhao%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Perez%20WB%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Lockhart%20SR%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sobel%20JD%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sobel%20JD%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Farmakiotis%20D%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kontoyiannis%20DP%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sanglard%20D%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Taj-Aldeen%20SJ%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Taj-Aldeen%20SJ%5BAuthor%5D&cauthor=true&cauthor_uid=27020939

https://www.ncbi.nlm.nih.gov/pubmed/?term=Alexander%20BD%5BAuthor%5D&cauthor=true&cauthor_uid=27020939



https://www.ncbi.nlm.nih.gov/pubmed/?term=Sershen%20SR%5BAuthor%5D&cauthor=true&cauthor_uid=14597719

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rivera%20B%5BAuthor%5D&cauthor=true&cauthor_uid=14597719

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rivera%20B%5BAuthor%5D&cauthor=true&cauthor_uid=14597719

https://www.ncbi.nlm.nih.gov/pubmed/?term=Price%20RE%5BAuthor%5D&cauthor=true&cauthor_uid=14597719

https://www.ncbi.nlm.nih.gov/pubmed/?term=Hazle%20JD%5BAuthor%5D&cauthor=true&cauthor_uid=14597719

https://www.ncbi.nlm.nih.gov/pubmed/?term=Halas%20NJ%5BAuthor%5D&cauthor=true&cauthor_uid=14597719

https://www.ncbi.nlm.nih.gov/pubmed/?term=West%20JL%5BAuthor%5D&cauthor=true&cauthor_uid=14597719

https://www.ncbi.nlm.nih.gov/pubmed/?term=Molina%20H%5BAuthor%5D&cauthor=true&cauthor_uid=26524530

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kohsaka%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26524530

https://www.ncbi.nlm.nih.gov/pubmed/?term=Di%20Giannatale%20A%5BAuthor%5D&cauthor=true&cauthor_uid=26524530

https://www.ncbi.nlm.nih.gov/pubmed/?term=Di%20Giannatale%20A%5BAuthor%5D&cauthor=true&cauthor_uid=26524530

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ceder%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26524530

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bakhti%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20404108

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gr%C3%B8nborg%20M%5BAuthor%5D&cauthor=true&cauthor_uid=20404108

https://www.ncbi.nlm.nih.gov/pubmed/?term=M%C3%B6bius%20W%5BAuthor%5D&cauthor=true&cauthor_uid=20404108

https://www.ncbi.nlm.nih.gov/pubmed/?term=M%C3%B6bius%20W%5BAuthor%5D&cauthor=true&cauthor_uid=20404108

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rhee%20J%5BAuthor%5D&cauthor=true&cauthor_uid=20404108

https://www.ncbi.nlm.nih.gov/pubmed/?term=Hu%20M%5BAuthor%5D&cauthor=true&cauthor_uid=17057837

https://www.ncbi.nlm.nih.gov/pubmed/?term=Chen%20J%5BAuthor%5D&cauthor=true&cauthor_uid=17057837

https://www.ncbi.nlm.nih.gov/pubmed/?term=Li%20ZY%5BAuthor%5D&cauthor=true&cauthor_uid=17057837

https://www.ncbi.nlm.nih.gov/pubmed/?term=Au%20L%5BAuthor%5D&cauthor=true&cauthor_uid=17057837

https://www.ncbi.nlm.nih.gov/pubmed/?term=Hartland%20GV%5BAuthor%5D&cauthor=true&cauthor_uid=17057837

https://www.ncbi.nlm.nih.gov/pubmed/?term=Li%20X%5BAuthor%5D&cauthor=true&cauthor_uid=17057837

https://www.ncbi.nlm.nih.gov/pubmed/?term=Marquez%20M%5BAuthor%5D&cauthor=true&cauthor_uid=17057837

https://www.ncbi.nlm.nih.gov/pubmed/?term=Marquez%20M%5BAuthor%5D&cauthor=true&cauthor_uid=17057837

https://www.ncbi.nlm.nih.gov/pubmed/?term=Xia%20Y%5BAuthor%5D&cauthor=true&cauthor_uid=17057837


https://www.ncbi.nlm.nih.gov/pubmed/?term=Lehto%20M%5BAuthor%5D&cauthor=true&cauthor_uid=25123235

https://www.ncbi.nlm.nih.gov/pubmed/?term=Savolainen%20K%5BAuthor%5D&cauthor=true&cauthor_uid=25123235

https://www.ncbi.nlm.nih.gov/pubmed/?term=Savolainen%20K%5BAuthor%5D&cauthor=true&cauthor_uid=25123235

https://www.ncbi.nlm.nih.gov/pubmed/?term=Savinko%20T%5BAuthor%5D&cauthor=true&cauthor_uid=25123235

https://www.ncbi.nlm.nih.gov/pubmed/?term=Alenius%20H%5BAuthor%5D&cauthor=true&cauthor_uid=25123235

https://www.ncbi.nlm.nih.gov/pubmed/?term=Banumathi%20B%5BAuthor%5D&cauthor=true&cauthor_uid=29169140

https://www.ncbi.nlm.nih.gov/pubmed/?term=Banumathi%20B%5BAuthor%5D&cauthor=true&cauthor_uid=29169140

https://www.ncbi.nlm.nih.gov/pubmed/?term=Govindarajan%20M%5BAuthor%5D&cauthor=true&cauthor_uid=29169140

https://www.ncbi.nlm.nih.gov/pubmed/?term=Alharbi%20NS%5BAuthor%5D&cauthor=true&cauthor_uid=29169140

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kadaikunnan%20S%5BAuthor%5D&cauthor=true&cauthor_uid=29169140

https://www.ncbi.nlm.nih.gov/pubmed/?term=Al-Anbr%20MN%5BAuthor%5D&cauthor=true&cauthor_uid=29169140

https://www.ncbi.nlm.nih.gov/pubmed/?term=Al-Anbr%20MN%5BAuthor%5D&cauthor=true&cauthor_uid=29169140


https://www.ncbi.nlm.nih.gov/pubmed/?term=Benelli%20G%5BAuthor%5D&cauthor=true&cauthor_uid=29169140

https://www.sciencedirect.com/science/journal/0304419X

https://www.sciencedirect.com/science/journal/0304419X

https://www.sciencedirect.com/science/journal/0304419X/1846/1

https://www.ncbi.nlm.nih.gov/pubmed/?term=Christensen%20IL%5BAuthor%5D&cauthor=true&cauthor_uid=18840487



Kang S, Herzberg M, Rodrigues DF, Elimelech M. (2008). Antibacterial effects of carbon nanotubes: size does matter! Langmuir. 24: 6409-6413.

Kim JS, Kuk E, Yu KN, Kim JH, Park SJ, Lee HJ, Jeong DH, Cho MH. (2007). Antimicrobial effects of silver nanoparticles. Nanomed. Nanotechnol. Biol. Med. 3: 95–101.

Kim S, Lee SY, Cho HJ. (2017). Doxorubicin-wrapped zinc oxide nanoclusters for the therapy of colorectal adenocarcinoma. Nanomaterials. 7(11): 354.

Klumpp C, Kostarelos K, Prato M, Bianco A. (2006). Functionalized carbon nanotubes as emerging nanovectors for the delivery of therapeutics. Biochim. Biophys. Acta. 1758: 404–412.

Kolodziejczak-Radzimska A, Jesionowski T. (2014). Zinc oxide–from synthesis to application: a review. Materials. 7(4): 2833–2881.

Kommareddy S, Amiji M. (2007). Poly(ethyleneglycol)-modified thiolated gelatin nanoparticles for glutathione-responsive intracellular DNA delivery. Nanomedicine. 3: 32–42.

Kitture R, Chordiya K, Gaware S, Ghosh S, More PA, Kulkarni P, Chopade BA, Kale SN. (2015). ZnO nanoparticles red sandalwood conjugate: a promising anti-diabetic agent. J. Nanosci. Nanotechnol. 15(6): 4046–4051.

Kosaka N, Iguchi H, Yoshioka Y, Hagiwara K, Takeshita F, Ochiya T. (2012). Competitive interactions of cancer cells and normal cells via secretory microRNAs. J. Biol. Chem. 287: 1397–1405.

Krishnamoorthy K, Manivannan G, Kim SJ, Jeyasubramanian K, Premanathan M. (2012). Antibacterial activity of MgO nanoparticles based on lipid peroxidation by oxygen vacancy. J. Nanoparticle. Res. 14: 1063.

Lamprecht C, Liashkovich I, Neves V, Danzberger J, Heister E, Rangl M, Coley HM, McFadden J, Flahaut E, Gruber HJ, et al. (2009). AFM imaging of functionalized carbon nanotubes on biological membranes. Nanotechnol. 20: 434001.

Landsdown ABG. (2002). Silver I: its antibacterial properties and mechanism of action. J. Wound. Care. 11: 125–138.

Lane RE, Korbie D, Anderson W, Vaidyanathan R, Trau M. (2015). Analysis of exosome purification methods using a model liposome system and tunable-resistive pulse sensing. Sci. Rep. 5: 7639.

Lawson C, Vicencio JM, Yellon DM, Davidson SM. (2016). Microvesicles and exosomes: new players in metabolic and cardiovascular disease. J. Endocrinol. 228: R57–R71.

Leonardo MR, Hernandez MEFT, Silva LAB, Tanomaru-Filho M. (2006). Effect of a calcium hydroxide-based root canal dressing on periapical repair in dogs: a histological study. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 102(5): 680–685.

Li Y, Zhang C, Liu L, Gong Y, Xie Y, Cao Y. (2017). The effects of baicalein or baicalin on the colloidal stability

of ZnO nanoparticles (NPs) and toxicity of NPs to Caco-2 cells. Toxicol. Mechanisms and Methods. 28(3): 167–176.

Liao H, Hafner JH. (2005). Gold nanorod bioconjugates. Chem. Mater. 17: 4636–4641.

Liao Y, Du X, Li J, Lönnerdal B. (2017). Human milk exosomes and their microRNAs survive digestion in vitro and are taken up by human intestinal cells. Mol. Nutr. Food. Res. 61(11). doi: 10.1002/mnfr.201700082.

Lima E, Guerra R, Lara V, Guzmán A. (2013). Gold nanoparticles as efficient antimicrobial agents for Escherichia coli and Salmonella typhi. Chem. Cent. J. 7: 11-17.

Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X, Dai H. (2008). Drug delivery with carbon nanotubes for in vivo cancer treatment. Cancer. Res. 68: 6652–6660.

Liu Z, Davis C, Cai W, He L, Chen X, Dai H. (2008). Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy. Proc. Natl. Acad. Sci. U S A. 105: 1410–1415.

Liu Z, Tabakman SM, Chen Z, Dai H. (2009). Preparation of carbon nanotube bioconjugates for biomedical applications. Nat. Protoc. 4: 1372–1382.

Loo C, Lin A, Hirsch L, Lee MH, Barton J, Halas N, West J, Drezek R. (2004). Nanoshell enabled photonics-based imaging and therapy of cancer. Technol. Cancer. Res. Treat. 3: 33–40.

Long M, Wang J, Zhuang H, Zhang Y, Wu H, Zhang J. (2014). Performance and mechanism of standard nano-TiO2 (P-25) in photocatalytic disinfection of food borne microorganisms—Salmonella typhimurium and Listeria monocytogenes. Food. Control. 39(1): 68–74.

Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D. (2017). Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta. Pharmacol. Sin. 38: 754–763.

Luo D, Saltzman WM. (2000). Synthetic DNA delivery systems. Nature. Biotech. 18: 33–37.

140. Luo Z, Ye -S, –Y Q, D –L. (2013). Influence of nano-TiO2 modified LDPE film packaging on quality of strawberry. Modern Food Sci. Technol. 29(10): 2340– 4, 2537.

Madani SY, Naderi N, Dissanayake O, Tan A, Seifalian AM. (2011). A new era of cancer treatment: carbon nanotubes as drug delivery tools. Int. J. Nanomed. 6: 2963–2979.

Malizia R, Scorsone A, D’Angelo P, Pinto CL, Pitrolo L, Giordano C. (1998). Zinc deficiency and cell-mediated and humoral autoimmunity of insulin-dependent diabetes in thalassemic subjects. J. Pediat. Endocrinol. Metabol: JPEM. 11(3): 981–984.

Manke A, Wang L, Rojanasakul Y. (2013). Mechanisms of nanoparticle-induced oxidative stress and toxicity. Biomed. Res. Int. 2013: 942916.

Maqusood A, Hisham AA, Majeed K, Ponmurugan K, Naif A. Al-D. (2014). Synthesis, Characterization, and Antimicrobial Activity of Copper Oxide Nanoparticles. J. Nanomaterials. 2014: Article ID 637858.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ghosh%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26369011

https://www.ncbi.nlm.nih.gov/pubmed/?term=More%20PA%5BAuthor%5D&cauthor=true&cauthor_uid=26369011

https://www.ncbi.nlm.nih.gov/pubmed/?term=More%20PA%5BAuthor%5D&cauthor=true&cauthor_uid=26369011

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kulkarni%20P%5BAuthor%5D&cauthor=true&cauthor_uid=26369011

https://www.ncbi.nlm.nih.gov/pubmed/?term=Chopade%20BA%5BAuthor%5D&cauthor=true&cauthor_uid=26369011

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kale%20SN%5BAuthor%5D&cauthor=true&cauthor_uid=26369011

https://www.ncbi.nlm.nih.gov/pubmed/?term=Danzberger%20J%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=Danzberger%20J%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=Heister%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=Rangl%20M%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=Coley%20HM%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=McFadden%20J%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=Flahaut%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=Flahaut%20E%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gruber%20HJ%5BAuthor%5D&cauthor=true&cauthor_uid=19801758

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sherlock%20S%5BAuthor%5D&cauthor=true&cauthor_uid=18701489

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cao%20Q%5BAuthor%5D&cauthor=true&cauthor_uid=18701489

https://www.ncbi.nlm.nih.gov/pubmed/?term=Chen%20X%5BAuthor%5D&cauthor=true&cauthor_uid=18701489

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dai%20H%5BAuthor%5D&cauthor=true&cauthor_uid=18701489

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dai%20H%5BAuthor%5D&cauthor=true&cauthor_uid=18701489


Saha and Bal 38

Marambio-Jones C, Hoek EMV. (2010). A review of the antibacterial effects of silver nanomaterials and potential implications for human health and the environment. J. Nanopart. Res. 12: 1531-1551.

Marcato PD, Duran N. (2008). New aspects of nanopharmaceutical delivery systems. J. Nanosci. Nanotechnol. 8: 2216–2229.

Mariko U, Mariko H-S, Kingo U, Yasuhide N. (2005). Photo-Control of the polyplexes formation between DNA and photo-cation generatable water-soluble polymers. Curr. Drug. Deliv. 2(3): 207–214.

Martinez-Carmona M, Gun’ko Y, Vallet-Regi M. (2018). ZnO nanostructures for drug, delivery and theranostic applications. Nanomaterials. 8(4): 268.

McIntosh CM, Esposito EA, Boal AK, Simard JM, Martin CT, Rotello VM. (2001). Inhibition of DNA transcription using cationic mixed monolayer protected gold clusters. J. Am. Chem. Soc. 123(31): 7626–7629.

Mishra PK, Mishra H, Ekielski A, Talegaonkar S, Vaidya B. (2017). Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications. Drug Discovery Today. 22(12): 1825–1834.

Moghaddam AB, Moniri M, Azizi S, Rahim RA, Ariff AB, Navaderi M, Mohamad, R. (2017). Eco-friendly formulated zinc oxide nanoparticles: induction of cell cycle arrest and apoptosis in the MCF-7 cancer cell line. Genes. 8(10): 281.

Moghimipour E, Rezaei M, Ramezani Z, Kouchak M, Amini M, Angali KA, Dorkoosh F A, Handali S. (2018). Transferrin targeted liposomal 5-fluorouracil induced apoptosis via mitochondria signaling pathway in cancer cells. Life. Sci. 194: 104–110.

Mohammadi Z, Dummer PMH. (2011). Properties and applications of calcium hydroxide in endodontics and dental traumatology. Int. Endodontic J. 44: 697–730.

Morones JR, Elechiguerra JL, Camacho A, Ramirez JT. (2005). The bactericidal effect of silver nanoparticles. Nanotechnology. 16: 2346–2353.

Murray AR, Kisin ER, Tkach AV, Yanamala N, Mercer R, Young SH, Fadeel B, Kagan VE, Shvedova AA. (2012). Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos. Part. Fibre. Toxicol. 9: 10.

Nagajyothi PC, Cha SJ, Yang IJ, Sreekanth TV, Kim KJ, Shin HM. (2015). Antioxidant and anti-inflammatory activities of zinc oxide nanoparticles synthesized using Polygala tenuifolia root extract. J. Photochem. Photobiol. B. 146: 10–17.

Nazarizadeh A, Asri-Rezaie S. (2016). Comparative study of antidiabetic activity and oxidative stress induced by zinc oxide nanoparticles and zinc sulfate in diabetic rats. AAPS. Pharm. Sci. Tech. 17(4): 834–843.

Newman MD, Stotland M, Ellis, JI. (2009). The safety of nanosized particles in titanium dioxide- and zinc oxide based sunscreens. J. Am. Acad. Dermatol. 61(4): 685–692.

Nguyen N-YT, Grelling N, Wetteland CL, Rosario R, Liu H. (2018). Antimicrobial Activities and Mechanisms of Magnesium Oxide Nanoparticles (nMgO) against

Pathogenic Bacteria, Yeasts, and Biofilms. Sci. Rep. 8: 16260.

Niidome T, Nakashima K, Takahashi H, Niidome Y. (2004). Preparation of primary amine-modified gold nanoparticles and their transfection ability into cultivated cells. Chem. Commun. 1978–1979.

Niidome Y, Niidome T, Yamada S, Horiguchi Y, Takahashi H, Nakashima K. (2006). Pulsed-laser induced fragmentation and dissociation of DNA immobilized on gold nanoparticles. Mol. Cryst. Liq. Cryst. 445: 201/[491]–206/[496].

Nirmala PN, Suresh G. (2013). Influence of the particle size on the optical properties of CaO thin film. Int. J. Rec. Sci. Res. 4:1320-1322.

Norman RS, Stone JW, Gole A, Murphy CJ, Sabo-Attwood TL. (2007). Targeted photothermal lysis of the pathogenic bacteria, Pseudomonas aeruginosa, with gold nanorods. Nano. Lett. 8: 302–306.

O'Gorman J, Humphreys H. (2012). Application of copper to prevent and control infection. Where are we now? J. Hosp. Infect. 81: 217-223.

Ohira T. Yamamoto O. (2012). Correlation between antibacterial activity and crystallite size on ceramics. Chem. Engineering Sci. 68(1): 355–361.

O'Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL. (2004). Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett. 209: 171–176.

Oosthuyzen W, Sime NE, Ivy JR, Turtle EJ, Street JM, Pound J, Bath LE, Webb DJ, Gregory C D, Bailey MA, Dear JW. (2013). Quantification of human urinary exosomes by nanoparticle tracking analysis: nanoparticle tracking analysis and exosomes. J. Physiol. 591: 5833–5842.

Othman SH, Salam NRA, Zainal N, Basha RK, Talib RA. (2014). Antimicrobial Activity of TiO2 Nanoparticle-Coated Film for Potential Food Packaging Applications. Int. J. Photoenergy. 2014: Article ID 945930.

Paciotti GF, Myer L, Weinreich D, Goia D, Pavel N, McLaughlin RE, Tamarkin L. (2004). Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery. Drug. Deliv. 11: 169–183.

Paciotti GF, Kingston DGI, Tamarkin L. (2006). Colloidal gold nanoparticles: a novel nanoparticle platform for developing multifunctional tumor-targeted drug delivery vectors. Drug. Dev. Res. 67: 47–54.

Pacurar M, Qian Y, Fu W, Schwegler-Berry D, Ding M, Castranova V, Guo NL. (2012). Cell permeability, migration, and reactive oxygen species induced by multiwalled carbon nanotubes in human microvascular endothelial cells. J. Toxicol. Environ. Health. A. 75: 129-147.

Pal S, Tak YK, Song JM. (2007). Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli. Appl. Environ. Microbiol. 27: 1712–1720.

Panacek A, Kvitek L, Prucek R, Kolar M, Vecerova R, Pizurova N, Sharma VK, Nevecna T, Zboril R. (2006).

https://www.ncbi.nlm.nih.gov/pubmed/?term=Abdul%20Rahim%20R%5BAuthor%5D&cauthor=true&cauthor_uid=29053567

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bin%20Ariff%20A%5BAuthor%5D&cauthor=true&cauthor_uid=29053567

https://www.ncbi.nlm.nih.gov/pubmed/?term=Navaderi%20M%5BAuthor%5D&cauthor=true&cauthor_uid=29053567

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kouchak%20M%5BAuthor%5D&cauthor=true&cauthor_uid=29275107

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kouchak%20M%5BAuthor%5D&cauthor=true&cauthor_uid=29275107

https://www.ncbi.nlm.nih.gov/pubmed/?term=Amini%20M%5BAuthor%5D&cauthor=true&cauthor_uid=29275107

https://www.ncbi.nlm.nih.gov/pubmed/?term=Angali%20KA%5BAuthor%5D&cauthor=true&cauthor_uid=29275107

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dorkoosh%20FA%5BAuthor%5D&cauthor=true&cauthor_uid=29275107

https://www.ncbi.nlm.nih.gov/pubmed/?term=Handali%20S%5BAuthor%5D&cauthor=true&cauthor_uid=29275107

https://www.ncbi.nlm.nih.gov/pubmed/?term=Fadeel%20B%5BAuthor%5D&cauthor=true&cauthor_uid=22490147

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kagan%20VE%5BAuthor%5D&cauthor=true&cauthor_uid=22490147

https://www.ncbi.nlm.nih.gov/pubmed/?term=Shvedova%20AA%5BAuthor%5D&cauthor=true&cauthor_uid=22490147

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bath%20LE%5BAuthor%5D&cauthor=true&cauthor_uid=24060994

https://www.ncbi.nlm.nih.gov/pubmed/?term=Webb%20DJ%5BAuthor%5D&cauthor=true&cauthor_uid=24060994

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gregory%20CD%5BAuthor%5D&cauthor=true&cauthor_uid=24060994

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bailey%20MA%5BAuthor%5D&cauthor=true&cauthor_uid=24060994

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bailey%20MA%5BAuthor%5D&cauthor=true&cauthor_uid=24060994

https://www.ncbi.nlm.nih.gov/pubmed/?term=Dear%20JW%5BAuthor%5D&cauthor=true&cauthor_uid=24060994

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sharma%20VK%5BAuthor%5D&cauthor=true&cauthor_uid=16913750

https://www.ncbi.nlm.nih.gov/pubmed/?term=Nevecna%20T%5BAuthor%5D&cauthor=true&cauthor_uid=16913750

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zboril%20R%5BAuthor%5D&cauthor=true&cauthor_uid=16913750



Silver colloid nanoparticles: synthesis, characterization, and their antibacterial activity. J. Phys. Chem. 110: 16248–16253.

Percival SL, Bowler PG, Dolman J. (2007). Antimicrobial activity of silver-containing dressings on wound microorganisms using an in vitro biofilm model. Int. Wound. J. 4: 186–191.

Pissuwan D, Valenzuela SM, Cortie MB. (2006). Therapeutic possibilities of plasmonically heated gold nanoparticles. Trends. Biotechnol. 24: 62–67.

Pissuwan D, Valenzuela SM, Killingsworth MC, Xu X, Cortie MB. (2007). Targeted destruction of murine macrophage cells with bioconjugated gold nanorods. J. Nanopart. Res. 9: 1109–1124.

Pissuwan D, Valenzuela SM, Cortie MB. (2008). Prospects for gold nanorod particles in diagnostic and therapeutic applications. Biotechnol. Gen. Eng. Rev. 25: 93–112.

Pissuwan D, Valenzuela SM, Miller CM, Killingsworth MC, Cortie MB. (2009). Destruction and control of Toxoplasma gondiitachyzoites using gold nanosphere/antibody conjugates. Small. 5: 1030–1034.

Porter AE, Gass M, Muller K, Skepper JN, Midgley PA, Welland M. (2007). Direct imaging of single-walled carbon nanotubes in cells. Nat. Nanotechnol. 2: 713–717.

Prado JV, Vidal AR, Duran TC. (2012). Application of copper bactericidal properties in medical practice. Rev. Med. Chil. 140: 1325-1332.

Prato M, Kostarelos K, Bianco A. (2008). Functionalized carbon nanotubes in drug design and discovery. Acc. Chem. Res. 41: 60–68.

Puvvada N, Rajput S, Prashanth Kumar BN, Sarkar S, Konar S, Brunt KR, Rao RR, Mazumdar A, Das SK, Basu R, Fisher PB, Mandal M, Pathak A. (2015). Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression. Sci. Rep. 5(1): article 11760.

Radt B, Smith TA, Caruso F. (2004). Optically addressable nanostructured capsules. Adv. Mat. 16: 2184–2189.

Raffa V, Ciofani G, Vittorio O, Riggio C, Cuschieri A. (2010). Physicochemical properties affecting cellular uptake of carbon nanotubes. Nanomedicine(Lond). 5: 89–97.

Raffi M, Mehrwan S, Bhatti TM, Akhter JI, Hameed A, Yawar W, Hasan MM. (2010). Investigations into the antibacterial behavior of copper nanoparticles against Escherichia coli. Ann. Microbiol. 60: 75-80.

Rai A, Prabhune A, Perry CC. (2010). Antibiotic mediated synthesis of gold nanoparticles with potent antimicrobial activity and their application in antimicrobial coatings. J. Mater. Chem. 20: 6789-6798.

Rai M, Yadav A, Gade A. (2009). Silver nanoparticles as a new generation of antimicrobials. Biotechnol. Adv. 27: 76–83.

Rajeshkumar S, Malarkodi C, Vanaja M, Gnanajobitha G, Paulkumar K, Kannan C Annadurai G. (2013). Antibacterial activity of algae mediated synthesis of

gold nanoparticles from Turbinaria conoides. Der. Pharma. Chemica. 5: 224-229.

Ranathunge TA, Karunaratne DGGP, Rajapakse RMG, Watkins DL. (2019). Doxorubicin Loaded Magnesium Oxide Nanoflakes as pH Dependent Carriers for Simultaneous Treatment of Cancer and Hypomagnesemia. Nanomaterials. 9: 208.

Rashed MH, Bayraktar E, Helal GK, Abd-Ellah MF, Amero P, Chavez-Reyes A, et al. (2017). Exosomes: From Garbage Bins to Promising Therapeutic Targets. Int. J. Mol. Sci. 18: 538-563.

Rasmussen JW, Martinez E, Louka P, Wingett DG. (2010). Zinc oxide nanoparticles for selective destruction of tumor cells and potential for drug delivery applications. Expert. Opinion. Drug. Deliv. 7(9): 1063–1077.

Ravishankar RV, Jamuna BA. (2011). Nanoparticles and their potential application as antimicrobials. Science against microbial pathogens: communicating current research and technological advances. A. Méndez-Vilas (Ed.) Mysore: Formatex; 2011: 197-209.

Reddy KM, Feris K, Bell J, Wingett DG, Hanley C, Punnoose A. (2007). Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems. Appl. Phys. Lett. 90(21):article 213902.

195. Rosca ID, Watari F, Uo M, Akasaka T. (2005). Oxidation of multiwalled carbon nanotubes by nitric acid. Carbon. 43(15): 3124-3131.

Rosemary MJ, MacLaren I, Pradeep T. (2006). Investigations of the antibacterial properties of ciprofloxacin@SiO2. Langmuir. 22: 10125–10129.

Roy K, Mao H-Q, Huanhg S-K, Leong KW. (1999). Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat. Med. 5: 387–391.

Ruparelia JP, Chatterjee AK, Duttagupta SP, Mukherji S. (2008). Strain specificity in antimicrobial activity of silver and copper nanoparticles. Acta. Biomater. 4: 707-716.

Ruszkiewicz JA, Pinkas A, Ferrer B, Peres TV, Tsatsakis A, Aschner M. (2017). Neurotoxic effect of active ingredients in sunscreen products, a contemporary review. Toxicology. Reports. 4: 245–259.

Rzigalinski BA, Strobl JS. (2009). Cadmium-Containing Nanoparticles: Perspectives on Pharmacology & Toxicology of Quantum Dots. Toxicol. Appl. Pharmacol. 238(3): 280–288.

Safavi KE, Nichols FC. (1993). Effect of calcium hydroxide on bacterial lipopolysaccharide. J. Endodontics. 19: 76.

Saha B, Bhattacharya J, Mukherjee A, Ghosh AK, Santra CR, Dasgupta AK, Karmakar P. (2007). In vitro structural and functional evaluation of gold nanoparticles conjugated antibiotics. Nanoscale. Res. Lett. 2: 614–622.

Sahoo S, Maiti M, Ganguly A, George JJ, Bhowmick AK. (2007). Effect of zinc oxide nanoparticles as cure activator on the properties of natural rubber and nitrile rubber. J. Appl. Polymer. Sc. 105(4): 2407–2415.

Sahoo NG, Bao H, Pan Y, Pal M, Kakran M, Cheng HK, Li L, Tan LP. (2011). Functionalized carbon nanomaterials as nanocarriers for loading and delivery

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sarkar%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26145450

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sarkar%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26145450

https://www.ncbi.nlm.nih.gov/pubmed/?term=Konar%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26145450

https://www.ncbi.nlm.nih.gov/pubmed/?term=Brunt%20KR%5BAuthor%5D&cauthor=true&cauthor_uid=26145450





https://www.sciencedirect.com/science/journal/00086223

https://www.sciencedirect.com/science/journal/00086223/43/15

https://www.ncbi.nlm.nih.gov/pubmed/?term=Pal%20M%5BAuthor%5D&cauthor=true&cauthor_uid=21451845

https://www.ncbi.nlm.nih.gov/pubmed/?term=Kakran%20M%5BAuthor%5D&cauthor=true&cauthor_uid=21451845

https://www.ncbi.nlm.nih.gov/pubmed/?term=Cheng%20HK%5BAuthor%5D&cauthor=true&cauthor_uid=21451845

https://www.ncbi.nlm.nih.gov/pubmed/?term=Li%20L%5BAuthor%5D&cauthor=true&cauthor_uid=21451845

https://www.ncbi.nlm.nih.gov/pubmed/?term=Li%20L%5BAuthor%5D&cauthor=true&cauthor_uid=21451845

https://www.ncbi.nlm.nih.gov/pubmed/?term=Tan%20LP%5BAuthor%5D&cauthor=true&cauthor_uid=21451845


Saha and Bal 40

of a poorly water-soluble anticancer drug: A comparative study. Chem. Commun. (Camb). 47: 5235–5237.

Salehi B, Mehrabian S, Ahmadi M. (2014). Investigation of antibacterial effect of Cadmium Oxide nanoparticles on Staphylococcus aureus bacteria. J. Nanobiotechnol. 12: 26.

Salem W, Leitner DR, Zingl FG. (2015). Antibacterial activity of silver and zinc nanoparticles against Vibrio cholerae and enterotoxic Escherichia coli. Int. J. Med. Microbiol. 305(1): 85–95.

Sarwar S, Chakraborti S, Bera S, Sheikh IA, Hoque KM, Chakrabarti P. (2016). The antimicrobial activity of ZnO nanoparticles against Vibrio cholerae: variation in response depends on biotype. Nanomed: Nanotechnol. Biol. Med. 12(6): 1499–1509.

Sarwar S, Ali A, Pal M, Chakrabarti P. (2017). Zinc oxide nanoparticles provide anti-cholera activity by disrupting the interaction of cholera toxin with the human GM1 receptor. J. Biol. Chem. 292(44): 18303–18311.

Savina A, Furlán M, Vidal M, Colombo MI. (2003). Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J. Biol. Chem. 278: 20083–20090.

Sawai J, Kojima H, Igarashi H, Hashimoto A, Shoji S, Sawaki T, Hakoda A, Kawada E, Kokugan T, Shimizu M. (2000). Antibacterial characteristics of magnesium oxide powder. World J. Microbiol. Biotechnolo. 16: 187–194.

Sawai J. (2003). Quantitative evaluation of antibacterial activities of metallic oxide powders (ZnO, MgO and CaO) by conductimetric assay. J. Microbiol. Methods. 54: 177-182.

Schey KL, Luther JM, Rose KL. (2015). Proteomics characterization of exosome cargo. Methods. 87: 75–82.

Seclen SN, Rosas ME, Arias AJ, Medina CA. (2017). Elevated incidence rates of diabetes in Peru: report from PERUDIAB, a national urban population-based longitudinal study. BMJ Open Diabetes Research and Care 5(1):article e000401.

Sershen SR, Westcott SL, Halas NJ, West JL. (2000). Temperature-sensitive polymer nanoshell composites for photothermally modulated drug delivery. J. Biomed. Mater. Res. 51: 293–298.

Shahverdi AR, Fakhimi A, Shahverdi HR, Minaian S. (2007). Synthesis and effect of silver nanoparticles on the antibacterial activity of different antibiotics against Staphylococcus aureus and Escherichia coli. Nanomedicine. 3:168–171.

Sharma V, Anderson D, Dhawan A. (2012). Zinc oxide nanoparticles induce oxidative DNA damage and ROS triggered mitochondria mediated apoptosis in human liver cells (HepG2). Apoptosis. 17(8): 852–870.

Shenoy D, Fu W, Li J, Crasto C, Jones G, Di Marzio C, Sridhar S, Amiji M. (2006). Surface functionalization of gold nanoparticles using hetero-bifunctional poly(ethyleneglycol) spacer for intracellular tracking and delivery. Int. J. Nanomedicine. 1: 51–57.

Shi LE, Li ZH, Zheng W, Zhao YF, Jin YF, Tang ZX. (2014). Synthesis, antibacterial activity, antibacterial mechanism and food applications of ZnO nanoparticles: a review. Food Additives and Contaminants: Part A. 31(2): 173–186.

Shiotani A, Mori T, Niidome T, Niidome Y, Katayama Y. (2007). Stable incorporation of gold nanorods into N-isopropylacrylamide hydrogels and their rapid shrinkage induced by near-infrared laser irradiation. Langmuir. 23: 4012–4018.

Shvedova AA, Pietroiusti A, Fadeel B, Kagan VE. (2012). Mechanisms of carbon nanotube-induced toxicity: focus on oxidative stress. Toxicol. Appl. Pharmacol. 261: 121-133.

Simons M, Raposo G. (2009). Exosomes – vesicular carriers for intercellular communication. Curr. Opin. Cell. Biol. 21: 575–581.

Singh BN, Rawat AK, Khan W, Naqvi AH, Singh BR. (2014). Biosynthesis of stable antioxidant ZnO nanoparticles by Pseudomonas aeruginosa rhamnolipids. PLoS One. 9(9): Article ID e106937.

Singh R, Nalwa HS. (2011). Medical applications of nanoparticles in biological imaging, cell labeling, antimicrobial agents, and anticancer nanodrugs. J. Biomed. Nanotechnol. 7: 489–503.

Skirtach AG, Javier AM, Kreft O, Köhler K, Alberola AP, Möhwald H, Parak WJ, Sukhorukov GB. (2006). Laser-induced release of encapsulated materials inside living Cells. Angew. Chem. 118: 4728–4733.

Smijs TG, Pavel S. (2011). Titanium dioxide and zinc oxide nanoparticles in sunscreens: focus on their safety and effectiveness. Nanotechnol. Sc. Applic. 4: 95–112.

Smith AM, Duan H, Mohs AM, Nie S. (2008). Bioconjugated quantum dots for in vivo molecular and cellular imaging. Adv. Drug. Delivery. Revs. 60: 1226–1240.

Sokolov VI, Stankevich IV. (1993). The fullerenes-new allotropic forms of carbon: molecular and electronic structure, and chemical properties. Russ. Chem. Rev. 62: 419.

Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, Barnes S, Grizzle W, Miller D, Zhang HG. (2010). A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcuminis enhanced when encapsulated in exosomes. Mol. Ther. 18: 1606–1614.

Suzuki R, Takizawa T, Negishi Y, Utoguchi N, Maruyama K. (2008). Effective gene delivery with novel liposomal bubbles and ultrasonic destruction technology. Int. J. Pharm. 354(1–2): 49–55.

Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD. (2016). Investigation of content, stoichiometry and transfer of miRNA from human neural stem cell line derived exosomes. PLoS ONE. 11: e0146353.

Stoimenov PK, Klinger RL, Marchin GL, Klabunde KJ. (2002). Metal oxide nanoparticles as bactericidal agents. Langmuir. 18: 6679–6686.

Stowe DF, Camara AKS. (2009). Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Singh%20R%5BAuthor%5D&cauthor=true&cauthor_uid=21870454

https://www.ncbi.nlm.nih.gov/pubmed/?term=Nalwa%20HS%5BAuthor%5D&cauthor=true&cauthor_uid=21870454

https://www.ncbi.nlm.nih.gov/pubmed/?term=Barnes%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20571541

https://www.ncbi.nlm.nih.gov/pubmed/?term=Barnes%20S%5BAuthor%5D&cauthor=true&cauthor_uid=20571541

https://www.ncbi.nlm.nih.gov/pubmed/?term=Grizzle%20W%5BAuthor%5D&cauthor=true&cauthor_uid=20571541

https://www.ncbi.nlm.nih.gov/pubmed/?term=Miller%20D%5BAuthor%5D&cauthor=true&cauthor_uid=20571541

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zhang%20HG%5BAuthor%5D&cauthor=true&cauthor_uid=20571541



Antioxidants and Redox Signaling. 11(6): 1373–1414. Takahashi H, Niidome Y, Yamada S. (2005). Controlled

release of plasmid DNA from gold nanorods induced by pulsed near-infrared light. Chem. Commun (Camb). 17: 2247–2249.

Takahashi H, Niidome T, Kawano T, Yamada S, Niidome Y. (2008). Surface modification of gold nanorods using layer-by-layer technique for cellular uptake. J. Nanopart. Res. 10: 221–228.

Takahito K, Yasuro N, Takeshi M, Yoshiki K, Takuro N. (2009). PNIPAM gel-coated gold nanorods for targeted delivery responding to a near-infrared laser. Bioconj. Chem. 20: 209–212.

Tan A, De La Pena H, Seifalian AM. (2010). The application of exosomes as a nanoscale cancer vaccine. Int. J. Nanomedicine. 5: 889–900.

Tang ZX, Lv BF. (2014). MgO Nanoparticles As Antibacterial Agent: Preparation And Activity. Braz. J. Chem. Eng. 31: 591–601.

Tanomaru JMG, Leonardo MR, Filho MT, Filho IB, Silva LAB. (2003). Effect of different irrigation solutions and calcium hydroxide on bacterial LPS. Int. Endodontic J. 36: 733.

Taylor DD, Zacharias W, Gercel-Taylor C. (2011). “Exosome isolation for proteomic analyses and RNA profiling,” in Serum/Plasma Proteomics, eds R. J. Simpson and D.W. Greening (Totowa, NJ: Humana Press), 235–246.

Thatoi P, Kerry RG, Gouda S, Das G, Pramanik K, Thatoi H, Patra JK. (2016). Photo-mediated green synthesis of silver and zinc oxide nanoparticles using aqueous extracts of two mangrove plant species, Heritiera fomes and Sonneratia apetala and investigation of their biomedical applications. J. Photochem. Photobiol. B. 163: 311–318.

The Nobel Prize in Physiology or Medicine. (2013). Available online at: http://www.nobelprize.org/nobel_ prizes/medicine/laureates/2013/ (Accessed March29, 2017).

Théry C, Zitvogel L, Amigorena S. (2002). Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2: 569.

Théry C, Amigorena S, Raposo G, Clayton A. (2006). “Isolation and characterization of exosomes from cell culture supernatants and biological fluids,” in Current Protocols in Cell Biology, eds J. S. Bonifacino, M. Dasso, J. B.Harford, J. Lippincott-Schwartz, and K. M. Yamada (Hoboken, NJ: JohnWiley& Sons, Inc.):1–29.

Thomas KG, Kamat PV. (2003). Chromophore-functionalized gold nanoparticles. Acc. Chem. Res. 36: 888–898.

Tian T, Zhang HX, He CP, Fan S, Zhu YL, Qi C, Huang NP, Xiao ZD, Lu ZH, Tannous BA, Gao J. (2018). Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy. Biomaterials. 150: 137–149.

Tickner JA, Urquhart AJ, Stephenson SA, Richard DJ, O’Byrne KJ. (2014). Functions and therapeutic roles of exosomes in cancer. Front. Oncol. 4: 127.

Tiwari DK, Behari J, Sen P. (2008). Application of Nanoparticles in Waste Water Treatment. World. Appl. Sci. J. 3: 417-433.

Tiwari PM, Vig K, Dennis VA, Singh SR. (2011). Functionalized gold nanoparticles and their biomedical applications. Nanomaterials. 1: 31-63.

Tiwari PK, Soo Lee Y. (2013). Gene delivery in conjunction with gold nanoparticle and tumor treating electric field. J. Appl. Phys. 114: 5.

Toncic RJ, Marinovic B. (2016). The role of impaired epidermal barrier function in atopic dermatitis. Acta. Dermatovenerologica. Croatica: ADC. 24(2): 95–109.

Tong L, Wei Q, Wei A, Cheng J-X. (2009). Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects. Photochem. Photobiol. 85: 21–32.

Umrani RD, Paknikar KM. (2014). Zinc oxide nanoparticles show antidiabetic activity in streptozotocin-induced Type 1 and 2 diabetic rats. Nanomedicine. 9(1): 89–104.

Usman MS, El Zowalaty ME, Shameli K, Zainuddin N, Salama M, Ibrahim NA. (2013). Synthesis, characterization, and antimicrobial properties of copper nanoparticles. Int. J. Nanomedicine. 8: 4467-4479.

Utreja P, Jain S, Tiwary AK. (2010). Novel drug delivery systems for sustained and targeted delivery of anti-cancer drugs: Current status and future prospects. Curr. Drug. Deliv. 7: 152–161.

Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ,

Lötvall JO. (2007). Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell. Biol. 9: 654–659.

Van der Meel R, Fens MH, Vader P, van Solinge WW, Eniola-Adefeso O, Schiffelers RM. (2014). Extracellular vesicles as drug delivery systems: lessons from the liposome field. J. Control. Release. 195: 72–85.

van der Pol E, Coumans FA, Grootemaat AE, Gardiner C, Sargent IL, Harrison P, Sturk A, van Leeuwen TG, Nieuwland R. (2014). Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flowcytometry, nanoparticle tracking analysis, and resistive pulse sensing. J. Thromb. Haemost. 12: 1182–1192.

Vasir JK, Reddy MK, Labhasetwar VD. (2005). Nanosystems in drug targeting: opportunities and challenges. Current. Nanosci. 1: 47–64.

Vecitis CD, Zodrow KR, Kang S, Elimelech M. (2010). Electronic-structure-dependent bacterial cytotoxicity of single-walled carbon nanotubes. ACS nano. 4: 5471-5479.

Vlassov AV, Magdaleno S, Setterquist R, Conrad R. (2012). Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim. Biophys. Acta. BBA. Gen. Subj. 1820: 940–948.

Wang J, Lee JS, Kim D, Zhu L. (2017). Exploration of zinc oxide nanoparticles as a multitarget and multifunctional

https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Tanomaru+Filho%2C+M

https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Bonetti+Filho%2C+I

https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Silva%2C+L+A+B

https://www.ncbi.nlm.nih.gov/pubmed/?term=Das%20G%5BAuthor%5D&cauthor=true&cauthor_uid=27611454

https://www.ncbi.nlm.nih.gov/pubmed/?term=Pramanik%20K%5BAuthor%5D&cauthor=true&cauthor_uid=27611454

https://www.ncbi.nlm.nih.gov/pubmed/?term=Thatoi%20H%5BAuthor%5D&cauthor=true&cauthor_uid=27611454

https://www.ncbi.nlm.nih.gov/pubmed/?term=Thatoi%20H%5BAuthor%5D&cauthor=true&cauthor_uid=27611454

https://www.ncbi.nlm.nih.gov/pubmed/?term=Patra%20JK%5BAuthor%5D&cauthor=true&cauthor_uid=27611454

https://www.ncbi.nlm.nih.gov/pubmed/?term=Huang%20NP%5BAuthor%5D&cauthor=true&cauthor_uid=29040874

https://www.ncbi.nlm.nih.gov/pubmed/?term=Huang%20NP%5BAuthor%5D&cauthor=true&cauthor_uid=29040874

https://www.ncbi.nlm.nih.gov/pubmed/?term=Xiao%20ZD%5BAuthor%5D&cauthor=true&cauthor_uid=29040874

https://www.ncbi.nlm.nih.gov/pubmed/?term=Lu%20ZH%5BAuthor%5D&cauthor=true&cauthor_uid=29040874

https://www.ncbi.nlm.nih.gov/pubmed/?term=Tannous%20BA%5BAuthor%5D&cauthor=true&cauthor_uid=29040874

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gao%20J%5BAuthor%5D&cauthor=true&cauthor_uid=29040874

https://www.ncbi.nlm.nih.gov/pubmed/?term=Sturk%20A%5BAuthor%5D&cauthor=true&cauthor_uid=24818656

https://www.ncbi.nlm.nih.gov/pubmed/?term=van%20Leeuwen%20TG%5BAuthor%5D&cauthor=true&cauthor_uid=24818656

https://www.ncbi.nlm.nih.gov/pubmed/?term=van%20Leeuwen%20TG%5BAuthor%5D&cauthor=true&cauthor_uid=24818656

https://www.ncbi.nlm.nih.gov/pubmed/?term=Nieuwland%20R%5BAuthor%5D&cauthor=true&cauthor_uid=24818656


Saha and Bal 42

anticancer nanomedicine. ACS. Applied Materials and Interfaces. 9(46): 39971–39984.

Wang J, Gan Y, Han P, Yin J, Liu Q, Ghanian S, Gao F, Gong G, Tang Z. (2018). Ischemia-induced Neuronal Cell Death Is Mediated by Chemokine Receptor CX3CR1. Sci. Rep. 8: 556.

Wang JT, Chen C, Wang E, Kawazoe Y. (2014). A new carbon allotrope with six-fold helical chains in all-sp2 bonding networks. Sci. Rep. 4: 4339.

Wang L, Hu C, Shao L. (2017). The antimicrobial activity of nanoparticles: present situation and prospects for future. Int. J. Nanomedicine. 12: 1227-1249.

West JL, Halas NJ. (2000). Applications of nanotechnology to biotechnology. Curr. Opin. Biotechnol. 11: 215–217.

West JL, Sershen SR, Halas NJ, Oldenburg SJ, Averitt RD. (2002). Temperature sensitive polymer/nanoshell composites for photothermally modulated drug delivery. US Patent 6428811;2002.

Wetteland CL, Nguyen N-YT, Liu H. (2016). Concentration-dependent behaviors of bone marrow derived mesenchymal stem cells and infectious bacteria toward magnesium oxide nanoparticles. Acta. biomaterialia. 35: 341–356.

Wiegand C, Hipler UC, Boldt S, Strehle J, Wollina U. (2013). Skin-protective effects of a zinc oxide-functionalized textile and its relevance for atopic dermatitis. Clin. Cosmetic. Investigational. Dermatol. 2013: 115–121.

Worst TS, von Hardenberg J, Gross JC, Erben P, Schnölzer M, Hausser I, et al. (2017). Database-augmented mass spectrometry analysis of exosomes identifies claudin 3 as a putative prostate cancer biomarker. Mol. Cell. Proteomics. MCP. 16: 998–1008.

Xiong HM. (2013). ZnO nanoparticles applied to bioimaging and drug delivery. Adv. Materials. 25(37): 5329–5335.

Yamanaka M, Hara K, Kudo J. (2005). Bactericidal actions of a silver ion solution on Escherichia coli, studied by energy-filtering transmission electron microscopy and proteomic analysis. Appl. Environ. Microbiol. 71: 7589–7593.

Yamashita S, Niidome Y, Katayama Y, Niidome T. (2009). Photochemical reaction of poly(ethylene glycol) on gold nanorods induced by near infrared pulsed-laser irradiation. Chem. Lett. 38: 226–227.

Yao N, Yeung KL. (2011). Investigation of the performance of TiO2 photocatalytic coatings. Chem Engineering J 167(1): 13–21.

Yang C, Mamouni J, Tang Y, Yang L. (2010). Antimicrobial activity of single-walled carbon nanotubes: length effect. Langmuir. 26: 16013-16019.

Yeh P, Perricaudet M. (1997). Advances in adenoviral vectors: from genetic engineering to their biology. FASEB J. 11: 615–623.

Yoon KY, Hoon Byeon J, Park JH, Hwang J. (2007). Susceptibility constants of Escherichia coli and Bacillus subtilis to silver and copper nanoparticles. Sci. Total Environ. 373: 572-575.

Zarei M, Jamnejad A, Khajehali E. (2014). Antibacterial Effect of Silver Nanoparticles Against Four Foodborne Pathogens. Jundishapur J. Microb. 7: E8720.

Zawrah MF, Abd El-Moez SI. (2011). Antimicrobial Activities of Gold Nanoparticles against Major Foodborne Pathogens. Life Sci. J. 8: 37-44.

Zhang H, Ma Y, Xie Y, An Y, Huang Y, Zhu Z, et al (2015) A Controllable aptamer-based self-assembled DNA dendrimer for high affinity targeting, bioimaging and drug delivery. Sci Rep 5:10099.

Zhang J, Qin X, Wang B, Xu G, Qin Z, Wang J, Wu L, Ju X, Bose DD, Qiu F, Zhou H, Zou Z. (2017). Zinc oxide nanoparticles harness autophagy to induce cell death in lung epithelial cells. Cell. Death. Dis. 8(7): article e2954.

Zhang X, Godbey WT. (2006). Viral vectors for gene delivery in tissue engineering. Adv. Drug Deliv. Rev. 58(4):515–534.

Zhang Y, Nayak TR, Hong H, Cai W. (2013). Biomedical applications of zinc oxide nanomaterials. Curr. Molec. Medicine. 13(10): 1633–1645.

Zhang ZY, Xiong HM. (2015). Photoluminescent ZnO nanoparticles and their biological applications. Materials. 8(6): 3101–3127.

Zheng K, Setyawati MI, Leong DT, Xie J. (2017). Antimicrobial gold nanoclusters. ACS Nano. 11: 6904-6910.

Zheng X, Chen F, Zhang J, Zhang Q, Lin J. (2014). Exosome analysis:a promising biomarker system with special attention to saliva. J. Membr. Biol. 247:1129–1136.

Zhou JJ, Wang SY, Gunasekaran S. (2009). Preparation and characterization of whey protein film incorporated with TiO2 nanoparticles. J. Food Sci. 74(7): N50–N56.

Zhou Y, Kong Y, Kundu S, Cirillo JD, Liang H. (2012). Antibacterial activities of gold and silver nanoparticles against Escherichia coli and bacillus Calmette-Guérin. J. Nanobiotechnol. 10: 19.

Zhu P, Weng Z, Li X, Liu X, Wu S, Yeung KWK, Wang X, Cui Z, Yang X, Chu PK. (2016). Biomedical applications of functionalized ZnO nanomaterials: from biosensors to bioimaging. Adv. Materials Interfaces. 3(1): article 1500494.

Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC, Ju S, Mu J, Zhang L, Steinman L, Miller D, Zhang HG. (2011). Treatment of Brain Inflammatory Diseases by Delivering Exosome Encapsulated Anti-inflammatory Drugs From the Nasal Region to the Brain. Mole. Ther. 19(10): 1769–1779.

Zinjarde SS. (2012). Bio-inspired nanomaterials and their applications as antimicrobial agents. Chronicles Young Scientists 3: 74-81.

Zonneveld M, Brisson AR, van Herwijnen MJ, Tan S, van de Lest CH, Redegeld FA, Garssen J, Wauben MH, Nolte-'t Hoen EN. (2014). Recovery of extracellular vesicles from human breast milk is influenced by sample collection and vesicle isolation procedures. J. Extra cell Vesicles. 3: 24215–24228.

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gao%20F%5BAuthor%5D&cauthor=true&cauthor_uid=29323156

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gao%20F%5BAuthor%5D&cauthor=true&cauthor_uid=29323156

https://www.ncbi.nlm.nih.gov/pubmed/?term=Gong%20G%5BAuthor%5D&cauthor=true&cauthor_uid=29323156

https://www.ncbi.nlm.nih.gov/pubmed/?term=Tang%20Z%5BAuthor%5D&cauthor=true&cauthor_uid=29323156

https://www.ncbi.nlm.nih.gov/pubmed/?term=Xu%20G%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Qin%20Z%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Wang%20J%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Wu%20L%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ju%20X%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ju%20X%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Bose%20DD%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Qiu%20F%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zhou%20H%5BAuthor%5D&cauthor=true&cauthor_uid=28749469

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zou%20Z%5BAuthor%5D&cauthor=true&cauthor_uid=28749469


https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Liu%2C+Xiangmei

https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Wu%2C+Shuilin

https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Wang%2C+Xianbao

https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Cui%2C+Zhenduo

https://onlinelibrary.wiley.com/action/doSearch?ContribAuthorStored=Yang%2C+Xianjin

https://www.ncbi.nlm.nih.gov/pubmed/?term=Ju%20S%5BAuthor%5D&cauthor=true&cauthor_uid=21915101

https://www.ncbi.nlm.nih.gov/pubmed/?term=Mu%20J%5BAuthor%5D&cauthor=true&cauthor_uid=21915101

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zhang%20L%5BAuthor%5D&cauthor=true&cauthor_uid=21915101

https://www.ncbi.nlm.nih.gov/pubmed/?term=Steinman%20L%5BAuthor%5D&cauthor=true&cauthor_uid=21915101

https://www.ncbi.nlm.nih.gov/pubmed/?term=Miller%20D%5BAuthor%5D&cauthor=true&cauthor_uid=21915101

https://www.ncbi.nlm.nih.gov/pubmed/?term=Zhang%20HG%5BAuthor%5D&cauthor=true&cauthor_uid=21915101

https://www.ncbi.nlm.nih.gov/pubmed/?term=Garssen%20J%5BAuthor%5D&cauthor=true&cauthor_uid=25206958

https://www.ncbi.nlm.nih.gov/pubmed/?term=Wauben%20MH%5BAuthor%5D&cauthor=true&cauthor_uid=25206958

https://www.ncbi.nlm.nih.gov/pubmed/?term=Wauben%20MH%5BAuthor%5D&cauthor=true&cauthor_uid=25206958

https://www.ncbi.nlm.nih.gov/pubmed/?term=Nolte-%27t%20Hoen%20EN%5BAuthor%5D&cauthor=true&cauthor_uid=25206958


Int. J. Res. Nanosci. Nanotechnol. 43 Accepted 20 June 2020 Citation: Saha B, Bal M (2020). Application of Nanomaterials in Medicine: Drug delivery, Diagnostics and Therapeutics. International Research Journal of Nanoscience and Nanotechnology, 2(1): 017-043.

Copyright: © 2020 Saha and Bal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are cited.

application of nanomaterials in medicine: drug delivery

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