Effect of molecular weight of chitosan and its oligosaccharides on antitumor activities of chitosan-selenium nanoparticles

Abstract

The antitumor activity of zero-valent selenium (Se⁰) nanoparticles stabilized by chitosan and its oligosaccharides having molecular weights 3 k, 65 k, and 600 k Da, was investigated. The nanoparticles stabilized with high molecular weight chitosan not only released selenium more easily compared with low molecular weight chitosan, but were also taken up by HepG2 cells more easily through electrostatic effect. Moreover, these were more efficient in inhibiting HepG2 cell viability. High ROS levels of cancer cells could easily induce selenium release from these nanoparticles, and oxidize the less toxic Se⁰ to highly toxic Se⁴⁺. The latter could not only consume antioxidant enzymes, but also cause mitochondrial dysfunction and cell apoptosis. Study of antitumor efficacy and side effect on a HepG2 xenograft BALB/c nude mice model exhibited that CS-Se⁰NPs had a higher selectivity for cancer cells; however, their effect on normal cells, which have relatively lower ROS levels, was limited.

Keywords: Antitumor; Chitosan; Electrostatic effect; Molecular weight; Selenium nanoparticle.