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

Angew Chem Int Ed Engl. 2022 Jun 27;61(26):e202204605. doi: 10.1002/anie.202204605. Epub 2022 May 3.

Abstract

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.

Keywords: Apoptosis; Ion Channels; K+ Transport; Light-Triggered Rotation; Molecular Motor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Ion Transport
  • Neoplasms*