Primary screening of the semiconductor nanoparticles in vivo

Primary screening of the semiconductor nanoparticles in vivo Dr. ZherdevaV., Dr. LoginovaY., Dr. Kazachkina N., Dr. Savitsky A. Bach Biochemistry Institute of Russian Academy of Science Moscow 2013

Quantum dots (QDs) - Semicondacter nanocrystal (1-10 nm) with unique photophysical properties : • Excitation in broad range of spectrum • emission depends on size • Lifetime of 20-40 ns • high extinction coefficient • high quantum yeild • uniqe photostability Semiconducter core: Cd/Se, Cd/Te, и Ga/N shell: Zn/S, Cd/Se biofunctional coating: polymer, protein or lipid

APPLICATION 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 usage… TOXIC or NON TOXIC? Distribution Localization and accumulation in vivo. per os Intravenously (i.v.)

TECHNOLOGY Type of administration • I.V. • Per os In vivoimaging Local fluorescence spectroscopy Localization study Confocal fluorescent microscopy Clinical biochemistry Toxical effects Morphology Pathomorphogy

QDs MPA • λem 611nm and 630 nm • d ~ 8 – 11нм • QY -10-20% QDs PolyT • λem 626 нм • d ~ 15 – 16 нм • QY 10-30% QY QDs PolyT-APS • λem 678 нм • d ~ 36 нм • QY 5-20%

FLUORESCENT EQUPMENT Laser spectrometer with optical zond iBox UVP

Monitoring of fluorescence in vivoin digestive tract of mice per os Excitation 502-547 nm, emission filter 570-640 nm exposition25с.

Local fluorescense spectroscopy No fluorescence(-), weak (±), high (+). Fluorescence of excrements after 24 h of QDs adminestering per os QDs MPA QDs PolyT QDs PolyT-APS Black line- excrements of control mice Red line- excrements of after QDs administering

I.V. QDs MPA LFS

I.V. QDs Poly T LFS

i.V. QDs PolyT-APS LFS

Confocal microscopy NB: weak+, medium ++, high +++, no -. (*)in blood vessel only Lungs Liver Lungs Liver а – reflecte lights, б – fluorescence, в – peudo color imaging, г – fluorescence spectra а

Toxicity of QDs MPA • Blood • Urea • creatinine, • alkaline phosphatase • alanine- and aspartate transaminases No change • Morphology Hihg spleen weight (twice) • Pathomorphology а б а – local haemorragia; б – stenosis of arteria.

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

conclusion Distribution and accumalation depend on the modification of coating Qds are dissolving in digestive tract: PolyT-APSare more stable comparing to QDs МPА andPolyT after per osadministering 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. 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

Локальная флуоресцентная спектроскопия (ЛФС)

Primary screening of the semiconductor nanoparticles in vivo