Effect of metallic nanoparticles on tumor growth: In vivo study.

e15650 Background: The aim of the study was to assess the effect of metallic nanoparticles on growth of transplanted ascitic tumor sarcoma 37 in mice. Methods: Nanoparticles (NP) of transition metals were experimentally developed and kindly provided us by Prof. V.B. Borodulin. Ultradispersed metallic powders (NP Cu, NP Zn, NP Fe) 30-100 nm sized were dispersed by ultrasound in 0.85% NaCl before use and daily administrated intraperitoneally to tumor-bearing mice with ascitic sarcoma 37. Injections of NP 500 µl (10 µg/ml) were performed for 4 days, and 4 days after the completion of the course mice were sacrificed. The control group received 0.85% NaCl. Ascitic fluid volume was measured and living cells were counted. Results: In all the tumor-bearing mice the progression of ascites was noted: it was maximal in controls, less in animals having received NP Fe and NP Cu, minimal – in mice after injection of NP Zn. The volume of the latter was 0.78±0.31 ml in comparison with control data: 1.79±0.66 ml (p < 0.05); it was also less than in mice after administration of NP Cu (2.16±0.68 ml) and NP Fe (3.3±1.3 ml). Similar difference was seen in the amount of tumor cells in ascitic fluid: (1.67±0.5)х106/ml after the injection of NP Zn and (27.7±2.86)х106/мл in the control group. Effect of NP Cu and NP Fe was less pronounced than of NP Zn though obvious in spite of the noted tendency of the increase of the ascitic fluid volume. The most significant changes were observed when absolute amount of living tumor cells was counted per one mouse – it was minimal after NP Zn administration (0.636±0.2)х106/ml and maximal in the control group (23.98±10.5)х106/ml), i.e. only 2.6% of tumor cells had survived after NP Zn injection. Conclusions: Our results demonstrate that metallic NP were able to produce antitumor in vivo without any supplements like laser or hyperthermia: the effect was likely to depend upon the metal and was the highest in NP Zn compared to NP Cu and Fe.

INFLUENCE OF INACTIVATION OF THE M-PROTEIN GENE ON ANTITUMOR ACTIVITY OF LIVE STREPTOCOCCUS PYOGENES IN EXPERIMENT

There was investigated a new recombinant strain of Streptococcus pyogenes serotype M39, which did not express M-protein - “Gurov” emm-. It revealed a higher antitumor activity towards transplantable solid murine tumors compared to wild type “Gurov”. In a model of sygeneic transplantable hepatoma 22a we observed retardation of tumor growth and increase of survival after twice intratumoral injections of live S. pyogenes “Gurov” emm- as compared to a group of mice that received injections of S. pyogenes “Gurov” as well as to a control group of mice without treatment. In a model of transplantable Sarcoma 37 we also observed retardation of tumor growth after the introduction of mutant strain but without positive effect on survival. Additionally, it was showed that “Gurov” emm- strain possessed a higher direct cytotoxic effect towards hepatoma 22а cell line in vitro as compared to wild type “Gurov”. Genetic modification of S. pyogenes “Gurov” strain attenuated its virulence and allowed to consider this strain as potent candidate for further studies and its possible application for oncolytic therapy in the future.