A Light-Driven Molecular Machine Controls K + Channel Transport and Induces Cancer Cell Apoptosis.
Huiting YangJinhao YiShihao PangKai YeZhicheng YeQi DuanZexin YanCheng LianYi YangLinyong ZhuDa-Hui QuChunyan BaoPublished in: Angewandte Chemie (International ed. in English) (2022)
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.