澳门大学王瑞兵团队报道了缺氧引发的超分子自由基诱导细胞内聚合用于肿瘤精准治疗。相关研究成果发表在2025年1月13日出版的《美国化学会杂志》。

尽管已经开发了各种用于抗肿瘤治疗的控释系统，但脱靶副作用仍然是一个持续的挑战。生物相容性物质的原位治疗合成提供了一种更安全、更精确的替代方案。

该研究提出了一种缺氧引发的超分子自由基系统，能够诱导细胞内聚合，从而破坏4T1细胞内的细胞骨架和细胞器。该系统利用葫芦素[7]脲（CB[7]）和苝二酰亚胺衍生物（PDI）的2:1超分子主客体复合物，称为PDI+2CB[7]，该复合物被肿瘤的缺氧和还原环境选择性还原，产生离域自由基阴离子。

CB[7]有效地稳定了这些阴离子，使PDI+2CB[7]复合物能够在4T1细胞内与甲基丙烯酸2-羟乙酯（HEMA）引发自由基聚合。由此产生的原位聚合显著破坏了肿瘤代谢，导致强烈的抗肿瘤反应，没有全身毒性。

该研究表明，稳定的内源性刺激诱导的超分子自由基可以引发细胞内聚合反应，在没有常规化疗药物的情况下实现选择性和有效的抗肿瘤治疗。

附：英文原文

Title: Hypoxia-Initiated Supramolecular Free Radicals Induce Intracellular Polymerization for Precision Tumor Therapy

Author: Mian Tang, Zhiqing Yang, Xingchen Tang, He Ma, Beibei Xie, Jiang-Fei Xu, Cheng Gao, David Bardelang, Ruibing Wang

Issue&Volume: January 13, 2025

Abstract: Despite the development of various controlled release systems for antitumor therapies, off-target side effects remain a persistent challenge. In situ therapeutic synthesis from biocompatible substances offers a safer and more precise alternative. This study presents a hypoxia-initiated supramolecular free radical system capable of inducing intracellular polymerization, thereby disrupting the cytoskeleton and organelles within 4T1 cells. The system utilizes a 2:1 supramolecular host–guest complex of cucurbit[7]uril (CB[7]) and perylene diimide derivative (PDI), termed PDI+2CB[7], which is selectively reduced by the tumor’s hypoxic and reducing environment to generate delocalized free radical anions. CB[7] effectively stabilizes these anions, enabling the PDI+2CB[7] complex to initiate free radical polymerization with 2-hydroxyethyl methacrylate (HEMA) inside the 4T1 cells. The resulting in situ polymerization significantly disrupts tumor metabolism, leading to a strong antitumor response without systemic toxicity. This study demonstrates that stable, endogenous stimulus-induced supramolecular free radicals can trigger intracellular polymerization reactions, achieving a selective and effective antitumor therapy without conventional chemotherapeutic agents.

DOI: 10.1021/jacs.4c14847

Source: https://pubs.acs.org/doi/full/10.1021/jacs.4c14847