Chemotaxis-based self-accumulation of surface-engineered mitochondria for cancer therapeutic improvement

Abstract Insufficient penetration of therapeutic agents into tumor tissues results in an inadequate distribution of the agents and lower intracellular concentrations, leading to drug resistance and treatment failure. Specific delivery of therapeutic agents to solid tumors followed by high penetration and durable retention would hold great promise to improve current chemotherapy. Particularly, a smart Janus-like surface-coated mitochondria system was well designed and developed, which could mimic the natural bacterial to use the glucose as the fuel to swim directional to the tumors and spontaneously penetrate the depth of tumor tissues and retained for quite a long time. Moreover, the delivered healthy mitochondria could help the apoptotic signal activation and transmission to enhance the therapeutic performance of commercial anti-cancer drugs, epirubicin. Different from other strategies, the modified mitochondria acted like natural biosystems to actively accumulate in the tumors following the glucose gradient in the microenvironment. We believe this unique organelle-material complex would serve as highly promising candidates to combat multidrug resistance in future chemotherapy.