EFFICIENCY AND SAFETY OF TARGETED DELIVERY SYSTEMS BASED ON SELENIUM NANOPARTICLES IN EXPERIMENTAL CARCINOGENESIS

The study examined selenium nanoparticles (SeNPs) synthesized by laser ablation. In vitro experiments on human colorectal carcinoma HT29 cell culture were used to study the activity of selenium nanoparticles in suppressing tumor cell growth using a laboratory MTT test with calculation of the IC50 value in comparison with liposomal doxorubicin. Acute toxicity of selenium nanoparticles was determined on white outbred laboratory mice with intraperitoneal and intravenous administration with an assessment of lethal doses LD100 and LD50. Antitumor activity of selenium nanoparticles was studied on C57Bl/6 mice, which were transplanted with MC38 colorectal adenocarcinoma subcutaneously into the left hind paw of the mouse at a concentration of 106 cells per mouse. Starting from day 5, mice in the 3 intervention groups were intraperitoneally injected with SeNPs at doses of 10 mg/kg and 1 mg/kg, solubilized in sterile saline. Animals in the control group received the same volume of saline. Injections of SNPs were performed once a day for 14 days. For 20 days after the start of the experimental exposure, the animals were weighed daily and the size of their tumors was measured using an electronic caliper. It was shown that the liquid nanoform of selenium suppresses tumor cell growth in a wide range of concentrations, the average inhibitory concentration IC50 was 5.2 × 10-6 M, which allows us to confirm the presence of antitumor activity of SNPs in colorectal cancer cell culture. When determining the acute toxicity of selenium nanoparticles, the calculated values of LD50 for intraperitoneal administration were 502 [430 ÷ 575] mg/kg; LD100 in mice for intravenous administration was 415 [355 ÷ 480] mg/kg, which corresponds to class 3 – moderately toxic substances according to international regulations. In mice of the experimental group, no significant differences from the control were observed until the 9th day of injections of both doses of selenium nanoparticles, but starting from the 10th day of injections, a decrease in tumor volumes was observed compared to the control, and already on the 12th day, noticeable inhibition of tumor growth was observed. Moreover, this indicator was 2-2.5 times less than in the control, and there were no significant differences between the two experimental groups receiving different doses of selenium nanoparticles. The obtained results allow us to suggest that selenium nanoparticles have their own antitumor effect.