Alexey N. Bashkatov, Georgy S. Terentyuk, Elina A. Genina, Daniil A. Chumakov, Artem G. Terentyuk, Vadim D. Genin, Valery V. Tuchin, Saratov State University Alla B. Bucharskaya, Galina N. Maslyakova, Nikita A. Navolokin, Saratov State Medical University Boris N. Khlebtsov, Nikolay G. Khlebtsov, IBPPM RAS, Saratov, Russia SFM'12 September 25-28, 2012, Saratov, Russia

After pioneering works of early 1980s, there is a significant and growing interest in developing laser therapy methods for cancer treatment These methods are based on mechanisms of selective damage of abnormal (target) cells in the manner that is safe for surrounding normal cells These methods use photochemical, photomechanical, and photothermal effects of laser interactions with cells and tissues

It was recently established that laser-induced local heating of cellular structures (through photothermal (PT) mechanisms), using either pulsed or continuous laser radiation and mediated by light-absorbing nanoparticles and microparticles, may provide precisely localized damage that can be limited to single cells Accumulation of light-absorbing nanoparticles in relatively transparent cells may enhance their optical absorption up to several orders of magnitude Thus, nanoparticles (NP) act as localized sources of laser-induced heat that can cause cell damage Even greater potential for selective damage of target (e.g., cancer) cells exists through integration of NPs allow specific targeting of the cells PT effects of continuous wave radiation (such as hyperthermia) are most effectively used in damaging relatively large areas of abnormal tissues However, despite apparent advantages of the laser nano- thermolysis, the full potential of this method has not been realized yet

Nanocomposite: Gold nanorods coated with silicon dioxide layer with hematoporphyrine molecules (Au-SiO 2 -Hp) (l=108±12 nm, d=75±6 nm) Experimental Animals:  Three white autbred rats with transplanted liver tumor were used  One rat served as a control  1 mL of the nanocomposite was injected 1 hr before the experiment by 0.2 mL every 1 min  The rats were anaesthetized with Zoletil 50 (Virbac, France) Irradiation:  Laser (LCS-T-12, Russia) with irradiation wavelength 808 nm, power 2 Wt, power density 2.3 Wt/cm 2 Monitoring:  Thermal imager (IRI4010, IRISYS, UK)  Thermocouple K-TYPE, USA) Histological study  Histilogical specimen were taken from the sides of the tumor after photothermolysis  Description of tumor tissue specimen was made with microscope МС 100 ХР (Micros, Austria) integrated with camera Canon РС 1107 (Canon Inc., Japan) in transmitted light mode with magnification ×200

TEM-imaging of nanocomposite Fluorescent spectra of aqueous haematoporphyrin solution (broken curve) and nanocomposite suspension (solid curve)

Experimental Setup: Laser (808 nm) Thermocouple Thermal imager Hot bench Rat Tumor

Temporal dependence of the tumor temperature measured with the thermal imager

Temporal dependence of the tumor temperature measured with the thermocouple

Histological specimens of liver cancer Liver cancer composed of lobules of various sizes which separated by thin layers of connective tissue. Tumor cells were oval-round and had eccentrically located nucleus. A significant part of the cytoplasm was occupied by large vacuoles containing mucus

Necrosis are in 30-50% of tumor area

Tumor cells with degenerative changes are preserved only in the subcapsular zone, necrosis are almost total (90-95% of tumor area)

 It is shown that under action of laser irradiation (808 nm) temperature of skin surface measured with the thermal imager increases from 34.2±1.5°C up to 58.1±0.23°C for rats with the tumors sensitized by the nanocomposite and up to 48.8°C for the control rat  Temperature in the depth of the tumors measured with the thermocouple increases from 31.5±2.1°C up to 43.5±2.1°C for the all rats. It can be explained by inaccuracy of thermocouple connection

 Grant # Network of Excellence for Biophotonics (PHOTONICS4LIFE) of the Seventh Framework Programme of Commission of the European Communities  Grants # and KO of Russian Foundation of Basis Research  Russian Federation governmental contacts , , , and 14.B