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

Although 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.