Positive surface charge enhances selective cellular uptake and anticancer efficacy of selenium nanoparticles

Surface charge plays a key role in cellular uptake and biological actions of nanomaterials. Selenium nanoparticles (SeNPs) are novel Se species with potent anticancer activity and low toxicity. This study constructed positively charged SeNPs by chitosan surface decoration to achieve selective cellular uptake and enhanced anticancer efficacy. The results of structure characterization revealed that hydroxyl groups in chitosan reacted with SeO ₃^2- ion to form special chain-shaped intermediates, which could be decomposed to form crystals upon reduction by ascorbic acid. The initial colloids nucleated and then assembled into spherical SeNPs. The positive charge of the NH₃⁺ group on the outer surface of the nanoparticles contributed to the high stability in aqueous solutions. Moreover, a panel of four human cancer cell lines were found to be susceptible to SeNPs, with IC₅₀ values ranging from 22.7 to 49.3 μM. Chitosan surface decoration of SeNPs significantly enhanced the selective uptake by endocytosis in cancer cells and thus amplified the anticancer efficacy. Treatment of the A375 melanoma cells with chitosan-SeNPs led to dose-dependent apoptosis, as evidenced by DNA fragmentation and phosphatidylserine translocation. Our results suggest that the use of positively charged chitosan as a surface decorator could be a simple and attractive approach to achieve selective uptake and anticancer action of nanomaterials in cancer cells.