杭州师范大学刘俊秋团队的一项最新研究报道了光开关超分子相互作用调节K⁺跨膜转运和癌细胞凋亡。这一研究成果发表在2025年3月20日出版的国际学术期刊《美国化学会杂志》上。

在此，小组提出了一种偶氮苯结合的单链随机杂多聚合物（RHPs）衍生的仿生K⁺通道P3，它可以在脂质体和癌细胞中在三种离子传输状态（“开”、“部分关闭”和“完全关闭”）之间切换。光调制两组超分子相互作用（(1)氢键和π -π相互作用）激活P3的构象调整；(2)主客体相互作用)实现这些开关，类似于控制活动的蛋白质机制。潜在的分子机制是P3中偶氮苯部分的光异构化及其与β-环糊精（β-CD）的络合，从而实现“一石（偶氮苯部分），两鸟（超分子相互作用）”的策略。机制研究表明，P3诱导大量的K⁺外排（在4分钟内下降50%）、内质网（ER）应激、Ca²⁺火花、活性氧（ROS）增强，最终导致严重的线粒体依赖性凋亡。这种NCPs样通道（P3）有望为更深入地了解NCPs的内部机制以及治疗癌症和其他疾病提供新的机会。

据介绍，天然通道蛋白（NCPs）具有多种离子转运模式，但通过人工离子转运系统复制这种特性仍然是一个巨大的挑战。

附：英文原文

Title: Photo-Switchable Supramolecular Interactions Regulate K+ Transmembrane Transport and Cancer Cell Apoptosis

Author: Cong Li, Yaqi Wu, Sheng Bao, Hui Li, Zhengwei Xu, Jing Yan, Xiaoxuan Yu, Lei He, Tianlong Zhang, Wang Liu, Shida Hou, Yang Zhang, Jiayun Xu, Tengfei Yan, Tingting Wang, Yi Yan, Junqiu Liu

Issue&Volume: March 20, 2025

Abstract: Natural channel proteins (NCPs) have numerous ion transport modes, but it remains a big challenge to replicate this trait by artificial ion transport systems. Herein, we present 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.

DOI: 10.1021/jacs.4c14583

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c14583