Nanocarrier mediated DOX/siRNA targeted co-delivery for synergistic treatment of cutaneous melanoma in outdoor athletes.

Athletes engaging in long-term and high-intensity outdoor exercise training are at high-risk for cutaneous melanoma (CM). Due to the limitations and side effects of traditional tumor treatment methods, it's difficult for athletes with CM to maintain athletic ability and prolong sport career. Targeted combination therapy based on nanocarriers is currently a promising method for achieving more satisfactory therapeutic effects. Herein, the folate-biotin-quaternized starch nanoparticles (FBqS NPs) were used as a co-loading platform to deliver doxorubicin (DOX) and siRNA into human malignant melanoma cell lines (A375 cells) in vitro. Compared with all other drug formulations at the same drugs concentration, targeted siRNA/DOX/FBqS NPs exhibited the strongest cytotoxicity and inhibition capacity of proliferation and migration on A375 cells, while the cytotoxicity of blank FBqS NPs was almost negligible. Free folate in the culture medium could competitively inhibit the cytotoxicity of siRNA/DOX/FBqS NPs in dose-dependent manner. The endocytosis mediated by clathrin, caveolae and folate-receptor were the main pathways for A375 cells to swallow drug-loaded FBqS NPs. Therefore, the FBqS NPs were expected to achieve superior results in the combination treatment of chemotherapeutics and gene drugs for CM, which might be beneficial to athletes with CM.