北京师范大学杨清正团队揭示了超分子光敏剂实现不依赖氧生成羟基自由基用于光动力治疗。相关研究成果于2023年2月13日发表于国际顶尖学术期刊《美国化学会杂志》。

光动力疗法（PDT）高度依赖氧的性质限制了其在临床上对缺氧性实体瘤的治疗效果，这是一个亟待解决的问题。

该文中，研究人员开发了一种不依赖氧的超分子光动力剂，它通过在无氧条件下在细胞内富含丙酮酸的存在下氧化水来产生羟基自由基（OH）。设计了一种芴取代的BODIPY作为电子供体，并与苝二亚胺作为电子受体进行共组装，形成了四重氢键超分子光动力剂。详细的机理研究表明，光照射时分子间电子转移和电荷分离导致自由基离子对的有效生成。在无氧条件下，阳离子自由基直接氧化水生成高度细胞毒性的OH，阴离子自由基将电子转移到丙酮酸，实现催化循环。因此，这种光动力学试剂即使在严重缺氧环境下也表现出极好的光细胞毒性，并且对荷HeLa的小鼠模型具有极好的体内抗肿瘤效果。

该项工作为构建不依赖氧的光动力剂提供了一种策略，为有效的PDT对抗缺氧肿瘤开辟了一条途径。

附：英文原文

Title: Supramolecular Photosensitizer Enables Oxygen-Independent Generation of Hydroxyl Radicals for Photodynamic Therapy

Author: Kun-Xu Teng, Li-Ya Niu, Qing-Zheng Yang

Issue&Volume: February 13, 2023

Abstract: The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop an oxygen-independent supramolecular photodynamic agent that produces hydroxyl radical (OH) by oxidizing water in the presence of intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as the electron donor and coassembled with perylene diimide as the electron acceptor to form the quadruple hydrogen-bonded supramolecular photodynamic agent. Detailed mechanism studies reveal that intermolecular electron transfer and charge separation upon light irradiation result in an efficient generation of radical ion pairs. Under oxygen-free conditions, the cationic radicals directly oxidize water to generate highly cytotoxic OH, and the anionic radicals transfer electrons to pyruvic acid, realizing the catalytic cycle. Thus, this photodynamic agent exhibited superb photocytotoxicity even under severe hypoxic environments and excellent in vivo antitumor efficacy on HeLa-bearing mouse models. This work provides a strategy for constructing oxygen-independent photodynamic agents, which opens up an avenue for effective PDT against hypoxic tumors.

DOI: 10.1021/jacs.2c11868

Source: https://pubs.acs.org/doi/10.1021/jacs.2c11868