Novel Delivery of Sorafenib by Natural Killer Cell-Derived Exosomes-Enhanced Apoptosis in Triple-Negative Breast Cancer

Aim: We investigated the delivery of sorafenib (SFB) to breast cancer spheroids by natural killer cell-derived exosomes (NK-Exos). Methods: SFB-NK-Exos were constructed by electroporation. Their antitumor effects were evaluated by methyl thiazolyl tetrazolium, acridine orange/ethidium bromide, 4′,6-diamidino-2-phenylindole, annexin/propidium iodide, scratch and migration assay, colony formation, RT-PCR, western blot and lipophagy tests. Result: The loading efficacy was 46.66%. SFB-NK-Exos-treated spheroids showed higher cytotoxic effects (33%) and apoptotic population (44.9%). Despite the reduction of SFB concentration in the SFB-NK-Exos formulation, similar cytotoxic effects to those of free SFB were observed. Increased intracellular trafficking, sustained release of the drug and selective inhibitory effects demonstrated efficient navigation. Conclusion: This is the first report for SFB loading into NK-Exos, which led to significant cytotoxic intensification against cancer cells.