Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou, 510641, China.
J Mater Chem B. 2023 May 31;11(21):4600-4618. doi: 10.1039/d3tb00545c.
Photodynamic therapy (PDT) with an oxygen-dependent character is a noninvasive therapeutic method for cancer treatment. However, its clinical therapeutic effect is greatly restricted by tumor hypoxia. What's more, both PDT-mediated oxygen consumption and microvascular damage aggravate tumor hypoxia, thus, further impeding therapeutic outcomes. Compared to type II PDT with high oxygen dependence and high oxygen consumption, type I PDT with less oxygen consumption exhibits great potential to overcome the vicious hypoxic plight in solid tumors. Type I photosensitizers (PSs) are significantly important for determining the therapeutic efficacy of PDT, which performs an electron transfer photochemical reaction with the surrounding oxygen/substrates to generate highly cytotoxic free radicals such as superoxide radicals (˙O) as type I ROS. In particular, the primary precursor (˙O) would progressively undergo a superoxide dismutase (SOD)-mediated disproportionation reaction and a Haber-Weiss/Fenton reaction, yielding higher cytotoxic species (˙OH) with better anticancer effects. As a result, developing high-performance type I PSs to treat hypoxic tumors has become more and more important and urgent. Herein, the latest progress of organic type I PSs (such as AIE-active cationic/neutral PSs, cationic/neutral PSs, polymer-based PSs and supramolecular self-assembled PSs) for monotherapy or synergistic therapeutic modalities is summarized. The molecular design principles and strategies (donor-acceptor system, anion-π incorporation, polymerization and cationization) are highlighted. Furthermore, the future challenges and prospects of type I PSs in hypoxia-overcoming PDT are proposed.
光动力疗法（PDT）具有氧依赖性，是一种用于癌症治疗的非侵入性治疗方法。然而，其临床治疗效果受到肿瘤缺氧的极大限制。此外，PDT 介导的耗氧量和微血管损伤加剧了肿瘤缺氧，从而进一步阻碍了治疗效果。与高耗氧和高耗氧的 II 型 PDT 相比，I 型 PDT 耗氧量较低，具有克服实体瘤恶性缺氧困境的巨大潜力。I 型光敏剂（PS）对于确定 PDT 的治疗效果非常重要，它与周围的氧气/底物发生电子转移光化学反应，生成具有细胞毒性的自由基，如超氧自由基（˙O）作为 I 型 ROS。特别是，主要前体（˙O）会逐渐经历超氧化物歧化酶（SOD）介导的歧化反应和 Haber-Weiss/Fenton 反应，产生具有更好抗癌效果的更高细胞毒性物质（˙OH）。因此，开发用于治疗缺氧肿瘤的高性能 I 型 PS 变得越来越重要和紧迫。本文总结了用于单一疗法或协同治疗方式的有机 I 型 PS（如 AIE-活性阳离子/中性 PS、阳离子/中性 PS、基于聚合物的 PS 和超分子自组装 PS）的最新进展。重点介绍了分子设计原则和策略（供体-受体体系、阴离子-π 结合、聚合和阳离子化）。此外，还提出了 I 型 PS 在克服缺氧 PDT 中的未来挑战和前景。
