dr. zherdevav., dr. loginova y., dr. kazachkina n., dr. savitsky a. bach biochemistry institute of...

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Dr. ZherdevaV., Dr. Loginova Y., Dr. Kazachkina N., Dr. Savitsky A. Bach Biochemistry Institute of Russian Academy of Science Moscow 2013

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Dr. ZherdevaV., Dr. Loginova Y., Dr. Kazachkina N., Dr. Savitsky A.

Bach Biochemistry Institute of Russian Academy of ScienceMoscow

2013

Semiconducter core: Cd/Se, Cd/Te, и Ga/N

shell: Zn/S, Cd/Se

biofunctional coating:

polymer, protein or lipid

Excitation in broad range of spectrum

emission depends on size

Lifetime of 20-40 ns

high extinction coefficient

high quantum yeild

uniqe photostability

- Semicondacter nanocrystal (1-10 nm) with unique

photophysical properties :

APPLICATION OF QDSAPPLICATION OF QDS

Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, Sundaresan G, Wu AM, Gambhir SS, Weiss S: Quantum Dots for Live Cells, in Vivo Imaging, and Diagnositics. Science 2005 307(5709):538-544.

QDs is a perspective tools for medical QDs is a perspective tools for medical usage…usage…

TOXIC or NON TOXIC?TOXIC or NON TOXIC?

Distribution Localization and

accumulation in vivo.

Distribution Localization and

accumulation in vivo.

per os Intravenously (i.v.)

TECHNOLOGYTECHNOLOGY

Type of administration

•I.V.• Per os

Localization study

In vivo imaging

Local fluorescence spectroscopy

Confocal fluorescent microscopy

Pathomorphogy

Morphology

Clinical biochemistry

Toxical effects

QDs MPA• λ em 611nm and 630 nm• d ~ 8 – 11нм•QY -10-20%

QDs PolyT• λ em 626 нм• d ~ 15 – 16 нм•QY 10-30%

QDs PolyT-APS• λ em 678 нм• d ~ 36 нм•QY 5-20%

QY

FLUORESCENT EQUPMENT

iBox UVP Laser spectrometer with optical zond

Monitoring of fluorescence in vivoin digestive tract of mice

Excitation 502-547 nm, emission filter 570-640 nm exposition25с.

per osper os

QDsStomach after 2 h

Intenstines after 2 h

Intenstines after 4 h

Intenstines after 6 h

MPA + - - -

PolyT + + ± -

PolyT-APS + + + +No fluorescence (-), weak (±), high (+).

Local fluorescense spectroscopyLocal fluorescense spectroscopy

Fluorescence of excrements after 24 h of QDs adminestering per os

QDs MPA

Black line- excrements of control mice Red line- excrements of after QDs administering

QDs PolyT-APSQDs PolyT

I.V.I.V. QDs MPA

LFS

QDs Poly T

LFS

I.V.I.V.

i.V.i.V. QDs PolyT-APS

LFS

Confocal microscopyConfocal microscopyNB: weak+, medium ++, high +++, no -. (*)in blood vessel only

а – reflecte lights, б – fluorescence, в – peudo color imaging, г – fluorescence spectra

Lungs LiverLiverLungs

а – local haemorragia;

б – stenosis of arteria.

Blood Urea creatinine,

Morphology

Toxicity of QDs MPAToxicity of QDs MPA

No change

alkaline phosphatase alanine- and aspartate

transaminases

Hihg spleen weight (twice)

Pathomorphologyа б

I.V.I.V.QDs MPA toxicity: also depends on initial

solution

1. Distribution and accumalation depend on the modification of coating

2. Qds are dissolving in digestive tract: PolyT-APS are more stable comparing to QDs МPА and PolyT after per os administering

3. The main targeted organs for QDsМPА are the lungs, for PolyТ are the atria, for PolyT-APS are liver after I.V . Excretion of in the urine and faeces was not detected.

4. QDs of small size МPA stay in organism for a long period.They could lead to long-term pathomorphological changes in lungs on the 22-th day after administration.

5. The the severity of the toxic effect of QDs MPA depends on the solvent

CONCLUSIONCONCLUSION

Локальная флуоресцентная спектроскопия Локальная флуоресцентная спектроскопия (ЛФС)(ЛФС)