Photodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design and precise side-chain engineering to generate •O₂⁻ and •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed organic PS skeletons can generate electron-hole pairs to sensitize H₂O into •O₂⁻ and •OH under oxygen-free conditions with 808 nm photoexcitation, achieving NIR-photoexcited and oxygen-independent •O₂⁻ and •OH production. Further, compared with commonly used alkyl side chains, glycol oligomer as the PS side chain mitigates electron-hole recombination and offers more H₂O molecules around the electron-hole pairs generated from the hydrophobic PS skeletons, which can yield 4-fold stronger •O₂⁻ and •OH production, thus allowing an ultralow-power photoexcitation to yield high PDT effect. Finally, the feasibility of developing activatable PSs for tumor-specific photodynamic therapy in female mice is further demonstrated under 808 nm irradiation with an ultralow-power of 15 mW cm⁻². The study not only provides further insights into the PDT mechanism but also offers a general design guideline to develop an oxygen-independent organic PS using ultralow-power NIR photoexcitation for tumor-specific PDT.

光动力疗法（PDT）是一种有前途的癌症治疗方法，但由于其依赖于氧气和高功率密度光激发而具有局限性。在此，我们报道了基于聚合物的有机光敏剂（PS），通过合理的PS骨架设计和精确的侧链工程，在无氧条件下使用超低功率808 nm光激发产生·O ₂ ⁻和·OH，用于肿瘤特异性光动力消融。设计的有机PS骨架可以在无氧条件下通过808 nm光激发产生电子-空穴对，将H ₂ O敏化为•O ₂ ^-和•OH，实现近红外光激发和不依赖氧的•O ₂ ^-和•OH的生产。此外，与常用的烷基侧链相比，乙二醇低聚物作为 PS 侧链可减轻电子空穴复合，并在疏水性 PS 骨架生成的电子空穴对周围提供更多的 H ₂ O 分子，强度提高 4 倍。 O ₂ ^-和•OH 的产生，从而允许超低功率光激发产生高PDT 效果。最后，在15 mW cm ^-2超低功率的808 nm照射下，进一步证明了开发可激活PS用于雌性小鼠肿瘤特异性光动力治疗的可行性。该研究不仅提供了对 PDT 机制的进一步见解，还提供了使用超低功率近红外光激发进行肿瘤特异性 PDT 开发不依赖于氧的有机 PS 的总体设计指南。