Saratov Fall Meeting 2012

1. Photothermalandphotodynamiceffects at laser heating with gold nanoparticles and nanocomposits Au-SiO2-Hp Georgy S. Terentyuk1,3, Alla B. Bucharskaya1, Andrey V. Ivanov2, Elina A. Genina3, Alexey N. Bashkatov3, Irina L. Maksimova3, Valery V. Tuchin3, Boris N. Khlebtsov4, Nikolay G. Khlebtsov4 1Saratov State Medical University n. a. V.I. Razumovsky, Saratov 2Russian Cancer Research Center n. a. N.N. Blokhin , RAMS, Moscow 3Saratov State University n. a. N.G. Chernyshevsky, Saratov 4Institute of Biochemistry, Physiology of Plants, Microorganisms RAS, Saratov Saratov Fall Meeting 2012

2. Determination of gold by atomic absorption spectroscopy gold accumulation in organs control 15 nm 50 nm 160 nm 24 hrs after intravenous injection Au, μg/mL Atomic -adsorbtion Spectrometr AAS-3 (С. Zeiss) with lamp LT-6М Ashing с H2SO4 t=630оС Resonance line 242,8 nm Detection limit 0,02 μg/ml Range of the linear region 0,2-20,0 μg/ml blood brain kidneys lungs liver spleen Terentyuk et al. 2009, No. 5, 292-302

3. Dynamics of gold concentrations in tumor tissue intertwined after intravenous injection of gold nanoparticles Dynamics of gold concentration in blood after intravenous injection of gold nanoparticles Au, μg/mL t, min t, hrs ○- control, ●- tumor,  - skin and muscle tissue

4. The value of tumor vascularization for the passive delivery of nanoparticles

5. Size-dependent changes in the organs 24 hours after intravenous injection of gold nanoparticles brain blood separation

6. Setting resonances Transparency window of biological tissues Vis UV NIR Extinction Epidermis Dermis Hypodermis Wavelength, nm Gold nanoparticles synthesized in the laboratory of biosensors and nanoscale structures of IBPPM RAS, Saratov, Russia

7. Comparative dynamics of heating of gold nanoparticles solutions Temperature, oC 0.5 Wt/cm2 0.25 Wt/cm2 0.5 Wt/cm2 Time, min

8. The concentration of gold per gram of tissue a day after the intravenous administration Au, μg/g Au, μg/g control control tumor muscle control control liver spleen С – nanocages, R - nanorods

9. Laser thermolysisoftransplanted Ehrlich tumor in mice Intravenous 400 μg/mL intratumoral intravenous 720 μg/mL intravenous Intravenous 50 μg/mL 90 μg/mL T, °C T, °C control control Time of heating, min Time of heating, min

10. The maximum temperature on the surface after laser heating a b The kinetics of laser heating of the tumor (1) and health (2) tissues in its maximum one day after intravenous injection of gold nanorods at 2 (a) and 8 mg / kg (b). Curves 3 is the kinetics of maximum heating of healthy tissue without introducing nanoparticles (control)

11. The temperature distribution on the surface of the animal's skin with intravenous injection of nanoparticle - surface laser heating of the tumor T, °C 0 - before heating; 1-5 after 1-5 minutes after the start of heating, respectively; 6-8 after 1-3 minutes after the heating, respectively

12. Control - heating without nanoparticles, in a day Experiment - heating with nanoparticles in a day

13. Transplanted Ehrlich tumor -external irradiation experiment control 1 min 5 min 0 min

14. Interstitial hyperthermia with nanorods using a catheter with a fiber diffuser Р=1.5 Vtt=15 minL=10 mm

15. Pathology of tumor tissues aftercontrolled laser thermolysis using plasmon-resonant gold nanoparticles Tissue of transplanted rat kidney cancer before exposure hematoxylin-eosin stain Increase Х150 Without nanoparticles With gold nanoparticles Tumor tissue after laser exposure

16. Growth dynamics of subcutaneously transplanted kidney cancer in rats before and after laser hyperthermia, CW, 1 Watt, 30 min Laser action Tumor size, cm3 thermogram of tumor without nanoparticles A day after tumor transplantation ○ - control, ■ - laser heating without nanoparticles ▲ - laser heating after intravenous injection of nanoparticles, 1 ml  - laser heating after interstitial injection of nanoparticles, 0.2 mL thermogram of tumor interstitial introduction of nanoparticles to a depth of 7 mm

17. Dependence of the mean tumor volume on the number of days passed after PPTT Tumor volume, cm3 Number of days experimental groups with doses of administered gold nanorods: 8 (1) and 2 mg / kg (2), control groups under laser irradiation without introducing nanoparticles (3) and without laser irradiation (4)

18. Nanocomposites: vitrified gold-silver nanocages modified Yb-HP

19. Au-NR-SiO2-HP IR-laser ~2.3 Wt/cm2 He-Ne laser ~160 mWt/сm2 Tumor (20 min of exposure) Tumor before exposure (V= 3 сm3) Tumor after 72 hours (V= 0.16 сm3)

20. Three variants of the protocol for Au-NR-SiO2-HP PTD→12 hours→LTT a) absence of optical postthermal obstacles b)exclusion of thermal effects c) hemostasis (2-12 hours): it is benefit for thermotherapy as heat loss reduces d) decrease in the partial pressure of oxygen and pH increases thermal sensitivity e) LTT inhibits repair of necrotic cells • PTD + LTT • LTT accelerates chemical reactions • Synergistic effects on blood vessels (stasis, collapse) • Synchronicity subsequent processes in the tumor tissue LTT→24 hours→PDT a) direct necrosis b) hemostasis - partial reduction of oxygen and pH c) 24 hours restore of blood flow d) 24 hours - pic HSP70 e) resumption of protein synthesis 12-26 hours f) PDT inhibits repair of cells 1) the size of tumors < 3 cm3 2) Temperature 50-75 °C - to avoid the formation of coagulation optical barrier

21. Thank you!