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Home / Issues / № 2, 2014

Goroshinskaya I.A., Kachesova P.S., Borodulin V.B., Losev O.E., Polozhentsev O.E., Leonova А.V., Nemashkalova L.A.

Much attention in the development of new anticancer agents is given to the agents based on transition metals, many of which are essential. Since metals in nanoform have greater biological activity, we investigated the effect of copper nanoparticles (Cu NPs), iron (Fe NPs) and zinc (ZnO NPs) on the growth of transplanted tumors in rats - Sarcoma 45 (9.10-dimethyl-1.2-benzanthracene-induced fusiform cell fibrosarcoma, S-45) and Pliss’s lymphosarcoma (LSP). Nanoparticles were obtained from the coarse powder by plasma technology (particle size distribution of 20-80 nm). The elemental composition, morphology and homogeneity of NPs were investigated by X-ray absorption near edge spectroscopy, scanning electron microscopy and measuring zeta potential. 240 outbred white male rats weighing 220-250 g were used in experiments. Nanoparticles in 0.9% w/v of NaCl were injected intratumorally or intraperitonially (single dose 1.25 mg/kg) four times a week during two weeks with a week's break (8-fold administration). In control groups rats with S-45 or LSP received intraperitonially 0.3 ml of saline only. The effect of metal NPs on tumor growth was determined by the change in tumors volume and mass, percent inhibition of tumor growth by volume (Tv%), number of regression cases and morphological changes in the tumor tissue. Toxicity index and coefficient of endogenous intoxication were calculated by the ratio of the total and the effective albumin concentrations and the content of the molecules of average mass. The content of TBA active products (MDA) and the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPO) in erythrocytes as indicators of oxidative processes were determined by spectrophotometric methods.

According to data obtained administration of copper nanoparticles in a total dose of 10 mg/kg had the most pronounced effect in rat sarcoma 45, reaching 65.5% inhibition of tumor growth by volume (when administered intratumorally - 61%, after intraperitoneal administration of about 71%). In animals with Pliss’s lymphosarcoma antitumor action of copper nanoparticles significantly depended on the mode of administration: intratumoral administration was much more efficient – 77% and 50%, respectively. The introduction of iron nanoparticles in the same dose possessed similar antitumor effect in animals with Pliss’s lymphosarcoma and with sarcoma 45, intratumoral administration of nanosized metal was more effective on both models. In rats with LSP tumor regression was observed in 60% of animals, percentage of tumor growth inhibition was 66.3% for the tumor volume. In rats with S-45 Tv% was equal to 49.3%.

Moreover the introduction of copper and iron nanoparticles greatly reduced endogenous toxicity which is typical for cancer. Decrease in the toxicity index and the coefficient of intoxication occurred in all animals regardless of whether regression or continued tumor growth took place. The tendency to accumulate MDA was showed in the group of animals without effect, probably due to significant increase of SOD activity and reduced GPO activity compared with the control group. The SOD and GPO activity in the group with partial regressed LSP were not different from control group, but catalase activity was essentially increased. MDA level in this group was the lowest. Reduced in activity of hydrogen peroxide-reducing enzymes (catalase and GPO) was typical for the majority of animals with complete regression of the LSP. Thus, changes in the intensity of oxidative processes in the erythrocytes of the tumor-bearing animals are associated with the effect of copper and iron NPs on the tumor growth and did not depend on the mode of NPs administration.

However, introduction of ZnO NPs enhanced the growth of fibrosarcoma by about 50% in 60% of experimental animals independently of injection way. The other 40.0% of rats with S-45 showed delay in tumor growth or partial tumor regression. Quite a different pattern was observed when ZnO NPs were administered to animals with Pliss’s lymphosarcoma: the majority of animals demonstrated tumor growth inhibition or total regression of the tumor, which leads to increased survival of the tumor-bearing animals.

Thus, the antitumor effect of biogenic metal nanoparticles depends on the metal used, its mode of administration and the etiology of neoplasm that it is important to take into account in the study of these nanoparticles as potential anticancer agents. 

Bibliographic reference

Goroshinskaya I.A., Kachesova P.S., Borodulin V.B., Losev O.E., Polozhentsev O.E., Leonova А.V., Nemashkalova L.A. EFFECT OF BIOGENIC METALS NANOPARTICLES ON THE DEVELOPMENT OF TRANSPLANTED TUMORS IN RATS. International Journal Of Applied And Fundamental Research. – 2014. – № 2 –
URL: www.science-sd.com/457-24580 (24.08.2019).