1.D.337. The Photo-Switchable Interaction Regulated

K⁺ Transmembrane Transport (PSI-KTT) Family

Li et al. 2025 presented an azobenzene-incorporated single-chain random heteropolymers (RHPs)-derived biomimetic K⁺ channel P3, which can switch between three ion transport states ("ON," "Partially OFF," and "Totally OFF") in both liposomes and cancer cells. The conformational adjustments of P3 activated by light-modulating two groups of supramolecular interactions ((1) hydrogen bonding and π-π interactions; (2) host-guest interactions) realize these switches, resembling the protein mechanisms that govern activity. Underlying molecular mechanisms are the photoisomerization of azobenzene moieties in P3 and their complexation with β-cyclodextrin (β-CD), enabling the exploit of a "one stone (azobenzene moiety), two birds (supramolecular interactions)" strategy. Mechanistic investigations demonstrate that P3-induced substantial K⁺ efflux (a 50% drop within just 4 min) causes endoplasmic reticulum (ER) stress, intriguing Ca²⁺ sparks, enhanced reactive oxygen species (ROS), and finally severe mitochondria-dependent apoptosis. This NCP-like channel (P3) is expected to provide new opportunities for a deeper understanding of the internal mechanisms of NCPs, as well as for treating cancer and other diseases (Li et al. 2025).

References:

Li, C., Y. Wu, S. Bao, H. Li, Z. Xu, J. Yan, X. Yu, L. He, T. Zhang, W. Liu, S. Hou, Y. Zhang, J. Xu, T. Yan, T. Wang, Y. Yan, and J. Liu. (2025). Photo-Switchable Supramolecular Interactions Regulate K Transmembrane Transport and Cancer Cell Apoptosis. J. Am. Chem. Soc. 147: 14139-14153.