1. Photothermal and photodynamic effects 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
24 hrs after
intravenous injection
brain
kidneys
lungs
liver
spleen
blood
control
15 nm
50 nm
160 nm
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 ,02 μg/ml
Range of the linear region 0,2-20,0 μg/ml
Terentyuk et al. 2009, No. 5,

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. Transparency window of biological tissues
Setting resonances
Transparency window of biological tissues
Extinction
Wavelength, nm
Epidermis
Dermis
Hypodermis UV
Vis
NIR
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
Time, min
0.5 Wt/cm2
0.25 Wt/cm2

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

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

10. The maximum temperature on the surface after laser heatingb
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 Vt t=15 min L=10 mm

15. With gold nanoparticles
Pathology of tumor tissues after controlled 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. A day after tumor transplantation
Growth dynamics of subcutaneously transplanted kidney cancer in rats before and after laser hyperthermia, CW, 1 Watt, 30 min
Tumor size, cm3
A day after tumor transplantation
Laser
action
thermogram of tumor without nanoparticles
○ - 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 before exposure
(V= 3 сm3)
Tumor (20 min of exposure)
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 hours
f) PDT inhibits repair of cells
1) the size of tumors < 3 cm3
2) Temperature °C - to avoid the formation of coagulation optical barrier

21. Thank you!