Efficacy Of Selenium Nanoparticles Administered Intraperitoneally For The Prevention Of Growth Of Cancer Cells In Peritoneal Cavity

Selenium has been recognized as an essential trace element that played an irreplaceable role in maintaining normal function, regulating metabolization, confronting oxidative stress in mammalian species. The biological activity of selenium are associated with its chemical form, selenium in its valence state of zero is biologically inert, while selenium nanoparticles, prepared in our lab by the reaction of selenite and glutathione, and further dispersed by bovine serum albumin, is both stable and have similar bioavailability, with much lower toxicity as compared with other chemical forms of selenium. Thus challenges the long-held concept that selenium in its valence state of zero is biologically inert.Peritoneal implantation of cancer cells, particularly postoperative seeding metastasis, frequently occurs in patients with primary tumors in the stomach, colon, liver, and ovary. Peritoneal carcinomatosis is associated with poor prognosis. In the current work, we evaluated the prophylactic effect of intraperitoneal administration of selenium (Se), an essential trace element and a putative chemopreventive agent on peritoneal implantation of cancer cells.Elemental Se nanoparticles were injected into the abdominal cavity of mice, in which highly malignant H22 hepatocarcinoma cells had previously been inoculated. Se concentrations in the cancer cells and tissues, as well as the efficacy of proliferation inhibition and safety, were evaluated. Se was mainly concentrated in cancer cells when compared to Se retention in normal tissues, showing at least an order of magnitude difference between the drug target cells (the H22 cells) and the well-recognized toxic target of Se (the liver). Such a favorable selective distribution resulted in strong proliferation suppression without perceived host toxicity. The mechanism of action of the Se nanoparticles-triggered cytotoxicity was associated with Se-mediated production of reactive oxygen species, which impaired the glutathione and thioredoxin systems. Our results suggest that intraperitoneal administration of Se is a safe and effective means of preventing growth of cancer cells in peritoneal cavity for the above-mentioned high-risk populations.