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

• Published in: Carbohydrate polymers Vol. 231; p. 115689
• Main Authors: Song, Xiaoxiao, Chen, Yuying, Zhao, Guanghua, Sun, Hongbo, Che, Huilian, Leng, Xiaojing
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2020
• Subjects: Antitumor; Chitosan; Electrostatic effect; Molecular weight; Selenium nanoparticle; Selenium nanoparticle; Electrostatic effect; DMSO; XRD; Molecular weight; LDH; TUNEL; FTIR; Antitumor; CCK-8; XPS; BUN; CS-Se0NPs; GSH; 8-OHdG; PBS; ICP-AES; GSSG; BCA; AST; H&E; 2-DG; SOD; STEM; CS; DCFH-DA; MMP; Se; MEM; ROS; CAT; ALB; PI; Se0NPs; Chitosan; Se+4; Se0; JC-1
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2019.115689

[Display omitted] •The key roles of chitosan and its oligosaccharides were:•To regulate cell transmembrane behaviors of CS-Se0NPs by electrostatic effects.•To make CS-Se0NPs easily degraded by peroxides and release selenium.•To help to regulate the biofunctions of CS-Se0NPs by the Se0↔Se4+ redox cycle.•To regulate the above three properties by their molecular weight. 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.