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Nanocomposites for drug delivery in pathology place and for oncotherapy

Nanocomposites for drug delivery in pathology place and for oncotherapy. Alexander A. Golub Kyiv Taras Shevchenko National University Department of Inorganic Chemistry agolub@univ.kiev.ua. Fullerene C60 Biological Effects. Antivirus activity Antimicrobe activity Antitumor activity

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Nanocomposites for drug delivery in pathology place and for oncotherapy

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  1. Nanocomposites for drug delivery in pathology place and for oncotherapy Alexander A. Golub KyivTaras Shevchenko National University Department of Inorganic Chemistry agolub@univ.kiev.ua

  2. Fullerene C60 BiologicalEffects • Antivirus activity • Antimicrobe activity • Antitumor activity • Antioxidant activity • Chemotaxic activity • Prooxidant activity

  3. Fullerene behavior in biological objects Light Unharmed Tripletstate DNA annihilated

  4. Fullerene С60in a cell (А) Contrast image of MDA MB231cell, that absorb С60. Scale 20 mkm. (В) Picture of C60 aggregates under confocal microscope (red dots)

  5. Fullerene are forming colloid clusters 3-4 nm in diameter with icosahedra symmetry. The clusters are formed by 13 molecules of С60and the main part of cluster which is inside is not active. Colloid aggregation of C60 in water solutions Membrane transport: fast Biological transport: slow

  6. Minimization of fullerene С60concentration Enlargement of fullerene - substrate contact surface 3. Better biotransportation due to hydrophylic properties Replacement of inactive main part of fullerene cluster by hydrophilic SiO2nanoparticle Membrane transport: fast Biological transport: fast

  7. Hydrophilic fullerene nanosystems MModel of fullerene nanocomposite ТЕМ image of nanosilica particle ТЕМ imageof fullerene nanocomposite

  8. fluorescent antenna В А Fullerene nanocomposite with sensibilizer (fluorescent antenna) A- lateral contact, B- covalent contact. Photoluminescence spectra of fullerene nanocomposites with antracenalimin as fluorescent antenna A- fluorescent antenna at silica particle B- fluorescent antenna in lateral contact with fullerene C- fluorescent antenna in lateral contact and covalent contact with fullerene D- Fullerene nanocomposite Spironucleus vortenswith biomarker inside under microscope

  9. Intensification of peroxidation process in the cells Concentration ofAFKaccumulated in the cell in the presence of irradiated fullerenenanocomposite in cell solution: thymocyte, Erlich carcinoma and leukemia L1210 cells Accumulation of Shiff bases in the cell in the presence of irradiated fullerene thymocytes (А) Suspension of Erlih cells (В) 1- cells + 210-5mole С60,water solution 2- cells + 10-5Моль С60 nanocomposite 3- cells + 10-5Моль С60 nanocomposite with fluorescent antenna in lateral contact

  10. Fullerene nanocomposites with metal complexes Metal complex with fluorescence antenna in covalent contact with fullerene Photoluminescence peaks of fullerene nanocomposites with isoflavone antenna in different types of complexes Photoluminescence peaks of metal complexes of fullerene nanocomposites with different antennas

  11. Cytotoxicity of fullerene nanocomposites (% of viable cells in suspension) Not irradiated Irradiated 4 hours of incubation 4 hours of incubation C60-2*10-5 C60SiO2 C60SiO2+Antenna C60-2*10-5 C60SiO2 C60SiO2+Antenna 24 hours of incubation 24 hours of incubation C60-2*10-5 C60SiO2 C60SiO2+Antenna C60-2*10-5 C60SiO2 C60SiO2+Antenna

  12. Haemolytic effects Erythrocytesstability vshaemolysis time 1 without additives - control 2 with 210-5mole С60-SiO2 3 with 210-6mole С60-SiO2

  13. Anticancer activity in vivo Survival rate, % Day after inoculation of sarcoma 37

  14. Fullerene nanocomposite’s impact on lymphocyte activity note: * - р<0,05 cytotoxic index, % cytotoxic index, % day day cytotoxic activity antibody-dependentcytotoxic activity Fullerene nanocomposite increase cytotoxic index

  15. Fullerene nanocomposite’s impact on macrophages activity antibody-dependent  activity activity of macrophages Note: * - р<0,05 cytotoxic index, % cytotoxic index, % day day The increase in cytotoxic index was observed on 21 and 28 day after inoculation of sarcoma 37

  16. Absolute longevity index of animals with innoculated Sarcoma 37 1 – control, 2 – FIFA, 3 – АІFА, 4 – Zn2+АІFА, 5 – Cu2+СІFА, 6 – FА. Note: after 131 dayin groupFА in 43% animals, in group АІFА in 13% animals ingroups FІFА and Cu2+СІFА in 17% animalscancer was notevolved.

  17. Lewis lung carcinoma metastasis and C60 nanocomposite С60- SiO2 influence on metastases volume С60- SiO2 influence on Cytotoxic Index

  18. Active nancomposite transport

  19. Thanks

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