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

Yaqi Wu, Cong Li, Yanliang Wu, Jiayun Xu, Zhigang Ni, Ofer Reany, Tengfei Yan, Dingcheng Zhu, Junqiu Liu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalAdvanced Functional Materials
DOIs
StateAccepted/In press - 2024

Bibliographical note

Publisher Copyright:
© 2024 Wiley-VCH GmbH.

Keywords

  • high selectivity
  • ion interference therapy
  • ion transporters
  • K/Na-exchanger
  • photo-controlled

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