A Novel Detection Method for Atherosclerotic Lesions

Acknowledgments This work was financially supported by The Pennsylvania State

University, and co-sponsored by Dr. James Adair and Lawrence Sinoway

from the Hershey Medical Center.

Katherine Arazawa, Fara Foolad, Greg Lynn,

Kenny Surano, Samuel Vilchez Department of Biomedical Engineering

The Pennsylvania State University

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Cancers. ACS Nano, 1279-1287.

[2] Altnoglu, E., Russin, T., Kaiser, J., Barth, B., Eklund, P., Kester, M., & Adair, J. (2008). Near-Infrared Emitting Fluorophore-Doped Calcium Phosphate

Nanoparticles forImaging of Human Breast Cancer. ACS Nano, 2075-

2084.

Magnetite nanoparticles can serve as a multimodal imaging agent for identification of different stages of coronary artery

diseases.

Bio-conjugation to specific molecules serve to identify the stage of the disease

Images taken with a near infrared camera through various

filters showed that nanoparticles containing ICG fluoresce when

irradiated with a 785 nm laser. This fluorescence is then able to

penetrate bovine blood, showing promise these particles can be

detected using near infrared imaging when used as a targeting

agent.

Future Studies Ex vivo/in vivo studies, Imaging tests, Cytotoxicity, Degradability

To design a mechanism by which to use magnetite nanoparticles

as a multimodal contrast agent to identify the location of

atherosclerotic lesions in patients with coronary artery disease

(CAD).

Objective

Figure 1. Location of coronary arteries in heart

Coronary artery disease claims the lives of over 370,000 people every year in the United States alone.

Physicians lack an effective and economical method of detecting CAD in patients who are not exhibiting any

symptoms.

Considering many CAD patients do not display symptoms until a major occurrence such as a heart attack, it is vital that

physicians are provided with a method of detecting CAD in its

early stages.

Figure 2. Progression of atherosclerosis in CAD Weldon, 2015

CDC, 2013

Background

Imaging

Magnetite nanoparticles (NP) with indocyanine green (ICG)

fluorescent serve as a

multimodal imaging agent.

A simple and cost effective near infrared (NIR) imaging device

can be used to detect the ICG.

MRI or CT can be used to take high resolution images of the

atherosclerotic lesion if

accumulation is detected near

the heart

Targeting

Conjugating biomarkers to the surface of the NP that are

specific to these lesions will

increase the affinity of the NP to

the target site.

Targeting the progression of the lesions can be accomplished by

using various biomarkers

specific to different stages of the

disease.

Figure 3. The multimodal imaging

nanoparticle consists of ICG encapsulated

in calcium phosphosilicate conjugated to

the surface of a magnetite core.

Early stage:

high lipid concentration

Middle stage:

high macrophage concentration

Late stage:

hematoma and thrombus

Tyrosine LDL

tPA Fibrin

Anti-MSR1 MSR1

Concept

Bioconjugation schemes were created to bind the target

molecules to the magnetite nanocomplexes. Each scheme takes

advantage of either sulfhydryl or amine chemistry to bind through

a citrate-PEG linkage. To show a proof-of-concept, nanoparticles

were excited by a 785 nm laser to fluoresce near-infrared light

toward a camera. Light fluoresced through standard cuvettes

filled with water, fetal bovine serum, and bovine blood

respectively.

Figure 4. Anti-MSR1 (middle stage)

bioconjugation scheme using maleimide &

cysteine.

Experimental Procedure

Results

Conclusions

Photodiode

power meter

785 nm

laser diode

Blood in Optical Cuvette

20 cm

Optical table

Figure 5. Optical test setup

Figure 6. Images of (a) bovine blood (b) bovine blood with free ICG (c) bovine blood with

ICG encapsulated nanoparticles through 850 nm filter