A Light-Driven Molecular Machine Controls K+ Channel Transport and Induces Cancer Cell Apoptosis

The design of artificial ion channels with high activity, selectivity and gating function is challenging. Herein, we designed the light-driven motor molecule MC2, which provides new design criteria to overcome these challenges. MC2 forms a selective K+ channel through a single molecular transmembrane mechanism, and the light-driven rotary motion significantly accelerates ion transport, which endows the irradiated motor molecule with excellent cytotoxicity and cancer cell selectivity. Mechanistic studies reveal that the rotary motion of MC2 promotes K+ efflux, generates reactive oxygen species and eventually activates caspase-3-dependent apoptosis in cancer cells. Combined with the spatiotemporally controllable advantages of light, we believe this strategy can be exploited in the structural design and application of next-generation synthetic cation transporters for the treatment of cancer and other diseases.

Automated summary

In this study, a light-driven motor molecule called MC2 was designed to overcome the challenges of high activity, selectivity, and gating function in artificial ion channels. MC2 forms a selective K+ channel through a single molecular transmembrane mechanism, and its light-driven rotary motion increases ion transport, resulting in excellent cytotoxicity and cancer cell selectivity. Mechanistic studies showed that the rotary motion of MC2 promotes K+ efflux, generates reactive oxygen species, and activates caspase-3-dependent apoptosis in cancer cells. This strategy, combined with the advantages of light control, can be applied in the design and application of next-generation synthetic cation transporters for the treatment of cancer and other diseases.