A Reversible Light‐Driven Biomimetic K+/Na+‐Exchanger Controls Cancer Cell Apoptosis

Abstract

AbstractAlthough natural dual‐ion exchangers are indispensable for bio‐organic functions, developing their artificial counterparts remains nearly unexplored. Herein, this work proposes a novel light‐controlled K+/Na+‐transport‐exchanger TE12, realizing an unprecedented reversible switch between K+‐ and Na+‐transmembrane transport by changing its transport mechanism (channel and carrier). The conformational transformation of the azobenzene moiety in TE12 essentially induces this. The K+/Na+ selectivity of K+‐channel Trans‐TE12 is as high as 20.3, making it one of the most selective artificial K+‐transporters. Moreover, considering the scarcity of artificial Na+‐transporters, the Na+‐carrier Cis‐TE12 with high Na+/K+ selectivity (9.25) represents a breakthrough. Cis‐TE12 significantly triggers cell apoptosis by igniting fascinating “Na+ sparks” first observed on cancer cells treated with synthetic channels, while K+‐channel Trans‐TE12 exhibits low toxicity. Importantly, TE12 can function as a spatiotemporally controllable ion interference therapy, enabling in situ 365 nm light‐triggered and 450 nm light‐inhibited cell death. This work realizes sophisticated functions in a simplified structure by the “Less is More” design concept. It opens a shortcut toward the future iterative updating of artificial ion transporters to make them better biological analogs and therapeutic agents.