Liposomal valinomycin mediated cellular K+ leak promoting apoptosis of liver cancer cells

Abstract

Most cancer therapies are suffering from side effects to varying degrees, which might compromise the body functions and long-term health of patients. Balancing treatment efficacy and side effects has become a priority. Inspired by the concept that cellular ion homeostasis can lead to apoptosis, we developed a novel therapeutic strategy by incorporating the K+ transporter valinomycin into liposomes (Lipo-VM). Valinomycin is a naturally occurring polypeptide showing good biodegradation in vivo with reduced long-term side effects. Lipo-VM facilitates the K+ efflux of cells and triggers a caspase-dependent pathway of apoptosis by causing the collapse of mitochondrial membrane potential. With the help of a liposome-based nano-delivery system, Lipo-VM shows enhanced cell uptake and accumulation at the tumor site, which results in significant inhibition of tumor growth in a liver cancer model. The proposed valinomycin-anchored liposome provides an efficient and safe approach for cancer therapy.