THE USE OF NANOCOMPOSITE PHOTOSENSITIZERS FOR CANCER THERAPY Georgy S. Terentyuk, Saratov State University, Saratov State Medical University, Russia Daniil S. Chumakov, Saratov State University, Russia Alla B. Bucharskaya, Saratov State Medical University, Russia Galina N. Maslyakova, Saratov State Medical University, Russia Elina A. Genina,Saratov State University, Russia Alexey N. Bashkatov, Saratov State University, Russia Nikolai G. Klebtsov, IBPPM RAS, Russia Boris N. Khlebtsov, IBPPM RAS, Russia

to evaluate the antitumor efficiency of nanophotosensitizers - gold nanorods modified with hematoporphyrin on transplanted rat tumors by morphological method PURPOSE OF THE RESEARCH TEM imaging of gold nanorods

Materials and methods 30 mature outbred male rats with transplanted cholangiocarcinoma line PC-1 (V≥10 cm 3 ) Gold nanorods coated silica and functionalized hematoporphyrin. Synthesized by seed-mediated technology in IBPPM RAS, Saratov (L= 102 ±12 nm, d= 75 ± 6 nm, r= 1,4 ± 0,2) Max extinction – 810 nm, 632 nm, optical density 20 4 experimental groups and control group of animals (6 animals per group) Intratumor injection of gold nanocomposites (2 ml) Simultaneous irradiation of two lasers with wavelengths of 808 nm and 630 nm, both lasers are focused on one area of the tumor tissue. The power density of near- infrared laser was 2.3 W/cm2. The power density of the red laser was 0.86 mW/cm2.

Animals with transplanted tumors were divided into groups: 1.Control group - without any exposure 2.Comparison group 1. Intratumoral administration of saline. Irradiation of near infrared laser. 3.Comparison group 2. Intratumoral administration of a suspension of nanocomposites. Irradiation only near- infrared laser. 4.Comparison group 3. Intratumoral administration of a suspension of nanocomposites. Only red laser irradiation. 5.Experienced group Intratumoral administration of a suspension of nanocomposites. Combined exposure of 2 lasers. A day later irradiation animals were removed from the experiment and morphological study of tumor biopsy was performed Design of experiment

Results: irradiation of near infrared laser Control group with transplanted cholangiocarxcinoma (x246,4) Comparison group 1. Irradiation of near infrared laser (x246,4) At only infrared laser irradiation the tumor keeps alveolar structure, the vessels of the connective interlayers are full-blooded and contain red blood cells. Nuclei of tumor cells have different sizes, the areas of necrosis is about 5% from total area ​​.

Results: intratumoral administration of nanocomposites. Comparison group 2. Only near- infrared laser irradiation (x246,4) Comparison group 3. Only red laser irradiation (x246,4) After photothermolysis with photosensitizers the vast fields of necrosis (up to 60%) and foci of neutrophil infiltration were observed in the tumor center. After photodynamic treatment marked necrotic changes were noted in the center in place of influence. The congestion in the vessels and the phenomenon of separation of blood in some vessels were observed. On the periphery of the tumor the necrotic changes are less pronounced, nucleus of tumor cells are stored.

Results: intratumoral administration of nanocomposites and combined exposure of 2 lasers After combined exposure of red and infrared lasers the extensive fields of necrosis (up to 80-95%)were noted in the center of tumor, foci of neutrophil infiltration was observed. On the periphery of the tumor the necrotic changes are less pronounced. Experienced group after combined irradiation (x 246,6)

Conclusions The combined therapy of tumor with use of nanocomposite photosensitizers for intensification of photothermolysis and photodinamic effects is more efficient than separate photodynamic and photothermal effects. The gold nanocomposites are attractive agents for combination therapy in cancer treatment.