A51: Metallic nanoparticles produce antiproliferative effect in various models of tumor growth

Abstract

Nanotechnologies are significant modern trend embracing various fields of science including biology and medicine. Investigations of biological activities of nanoparticles (NP) suggest perspectives of their application in oncology. The role of metals in metabolic processes in the organism is well known, but a few data are available about the activities of nanometals. Our aim was to study the effect of metallic nanoparticles on growth of xenografts of human lung cancer and transplanted mouse tumors. Nanoparticles (NP) are ultrasmall metallic pulvers of Zn, Cu, Fe (size 40–100 nm). NP effects on growth of xenografts of human lung carcinoma cultured in chambers were studied in a following way. Samples of lung cancer patients’ tumor were put into chambers made of plastic and filters with pores 230 nm size. Chambers were implanted into rats’ abdominal cavity and NP suspension was administered intraperitoneally 3 times during the incubation period (6 days). Control animals were injected with 0.85% NaCl solution. After incubation filters were processed and stained for microscopy; amount of injured cells was counted. The experimental study of the NP effect on growth of transplanted tumors was carried out in mice with sarcomas (S37 and S180). NP suspensions were administered paratumoraly in total dose 20 μg/mouse; control mice were injected with 0.85% NaCl solution. Dynamics of tumor growth (S37, S180), tumor histology and cytology (S37), survival and life-span of mice (S180) were assessed. The results of histologic study of lung cancer tissue grown in chambers during 6 days showed vast injury of tumor cells, the most significant after administration of NP Cu. The amount of damaged cells was 93.4 ± 1.09% after NP Cu injection, 66.3 ± 2.28% after NP Zn injection, 37.6 ± 1.82% after NP Fe injection and only 18.3 ± 0.87% in control samples. The effect was independent of the tumors’ histostructure (adenocarcinoma, squamous cell carcinoma). Injection of metallic NP to tumor-bearing mice caused tumor regression both of S37 and S180. It was followed by death or severe destruction of S37 cells in ascitic and solid components of the tumor, maximal damage seen after application of NP Zn, minimal one after use of NP Fe. Volume of ascitic fluid in control mice with S 37 was 1.8 ± 0.66 ml with (27.7 ± 2.86) × 106/ml of alive tumor cells; after administration of NP Zn the parameters were only 0.78 ± 0.3 ml and (1.67 ± 0.5) × 106/ml respectively (P < 0.05). Volume of solid tumor was (574 ± 95) mm3 in control animals while in mice receiving NP Zn it reached only(154 ± 88) mm3 (P < 0.05). Results of histologic study of S37 showed that injection of NP Zn and NP Cu caused advanced increase of damaged tumor cells’ percentage (71.7 ± 8.7% and 48.2 ± 5.6%, respectively vs 13.7 ± 2.3% in control group). NP Fe induced destruction of 21.7 ± 4.3% of S37 cells. Tumor regression up to complete one was found also in S 180-bearing mice, as well as 3-4-fold prolongation of animals’ life-span without any visible signs of toxicity after injection of all studied kinds of NP. Doubtless antitumor effect of metallic NP was demonstrated on various experimental models of tumor growth including human and animal malignant tumors. NP caused injury of lung cancer cells cultured in chambers. Local injection of metallic NP induced death and/or destruction of tumor cells, decrease of tumor volume, inhibition of tumor growth and significant prolongation of experimental animals’ life span. Effect of NP Zn was found to be the strongest in vivo while NP Cu showed the most cytotoxic effect on lung carcinoma xenografts.