Positive Surface Charge Enhances Selective Cellular Uptake and Anticancer Efficacy of Selenium Nanoparticles

摘要

Surface charge plays a key role in cellularnuptake and biological actions of nanomaterials. Seleniumnnanoparticles (SeNPs) are novel Se species with potentnanticancer activity and low toxicity. This study constructednpositively charged SeNPs by chitosan surface decoration tonachieve selective cellular uptake and enhanced anticancernefficacy. The results of structure characterization revealed thatnhydroxyl groups in chitosan reacted with SeO3n2− ion to formnspecial chain-shaped intermediates, which could be decomposednto form crystals upon reduction by ascorbic acid. The initial colloids nucleated and then assembled into spherical SeNPs.nThe positive charge of the NH3n+ group on the outer surface of the nanoparticles contributed to the high stability in aqueousnsolutions. Moreover, a panel of four human cancer cell lines were found to be susceptible to SeNPs, with IC50 values rangingnfrom 22.7 to 49.3 μM. Chitosan surface decoration of SeNPs significantly enhanced the selective uptake by endocytosis in cancerncells and thus amplified the anticancer efficacy. Treatment of the A375 melanoma cells with chitosan−SeNPs led to dosedependentnapoptosis, as evidenced by DNA fragmentation and phosphatidylserine translocation. Our results suggest that the usenof positively charged chitosan as a surface decorator could be a simple and attractive approach to achieve selective uptake andnanticancer action of nanomaterials in cancer cells.