Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Binhai New City, Fuzhou, China.
Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, Singapore.
Nat Commun. 2024 Jun 10;15(1):4943. doi: 10.1038/s41467-024-49311-z.
The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O to O by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.
由于光动力疗法（PDT）在缺氧微环境中固有的缺氧不耐受性，开发 I 型光敏剂（PS）非常重要。与 II 型 PS 相比，由于缺乏通用的分子设计策略，I 型 PS 的报道较少。本文报道了将典型的 II 型 PS 和天然底物香芹酚（CA）结合，可以显著促进 I 型途径，有效地生成超氧自由基（O）。详细的机制研究表明，CA 在光照下由 PS 产生的局部单线态氧激活为百里香醌（TQ）。TQ 作为有效的电子转移介体，通过基于电子转移的 I 型途径促进 PS 将 O 转化为 O。值得注意的是，三种经典的 II 型 PS 被用于证明所提出方法的普遍性。在体外缺氧条件下已经证明了针对金黄色葡萄球菌的 I 型 PDT。此外，这种偶联的光动力试剂在体内实验中对感染细菌的雌性小鼠表现出显著的杀菌活性，抗菌率达到 99.6%。在这里，我们展示了一种简单、有效、通用的方法，使传统的 II 型 PS 具有缺氧耐受性。
