Photodynamic therapy (PDT) — which combines light, oxygen and photosensitizers (PS) to generate reactive oxygen species — has emerged as an effective approach for targeted ablation of pathogenic cells with reduced risk of inducing resistance. Some organic PS are now being applied for PDT in the clinic or undergoing evaluation in clinical trials. A limitation of the first-generation organic PS was their potential off-target toxicity. This shortcoming prompted the design of constructs that can be activated by the presence of specific biomolecules — from small biomolecules to large enzymes — in the target cells. Here, we review advances in the design and synthesis of activatable organic PS and their contribution to PDT in the past decade. Important areas of research include novel synthetic methodologies to engineer smart PS with tuneable singlet oxygen generation, their integration into larger constructs such as bioconjugates, and finally, representative examples of their translational potential as antimicrobial and anticancer therapies.

光动力疗法 （PDT） — 结合光、氧和光敏剂 （PS） 以产生活性氧 — 已成为一种靶向消融病原细胞的有效方法，降低了诱导耐药性的风险。一些有机 PS 现在正在临床上用于 PDT 或在临床试验中进行评估。第一代有机 PS 的一个局限性是其潜在的脱靶毒性。这一缺陷促使设计了可以通过靶细胞中存在特定生物分子（从小生物分子到大酶）来激活的构建体。在这里，我们回顾了过去十年中可活化有机 PS 的设计和合成进展及其对 PDT 的贡献。重要的研究领域包括设计具有可调节单线态氧产生的智能 PS 的新型合成方法，将它们整合到更大的结构中，例如生物共轭物，最后，它们作为抗菌和抗癌疗法的转化潜力的代表性示例。