A singlet oxygen-storing covalent organic framework for “Afterglow” photodynamic therapy

Photodynamic therapy (PDT) is an emerging treatment but often restricted by the availability of oxygen. Enhancing the lifespan of singlet oxygen ( 1 O 2 ) by fractionated generation is an effective approach to improve the efficacy of PDT. Herein, an imine-based nanoscale COF (TpDa-COF) has been synthesized and functionalized with a pyridone-derived structure (Py) to create a 1 O 2 -storing nanoplatform TpDa-COF@Py, which can reversibly capture and release 1 O 2 . Under 660 nm laser exposure, Py interacts with 1 O 2 produced by the porphyrin motif in COF backbones to generate 1 O 2 -enriched COF (TpDa-COF@Py + hv), followed by the release of 1 O 2 through retro-Diels-Alder reactions at physiological temperatures. The continuous producing and releasing of 1 O 2 upon laser exposure leads to an "afterglow" effect and a prolonged 1 O 2 lifespan. In vitro cytotoxicity assays demonstrates that TpDa-COF@Py + hv exhibits an extremely low half-maximal inhibitory concentration (IC 50 ) of 0.54 µg/mL on 4T1 cells. Remarkably, the Py-mediated TpDa-COF@Py nanoplatform demonstrates enhanced cell-killing capability under laser exposure, attributed to the sustained 1 O 2 cycling, compared to TpDa-COF alone. Further in vivo assessment highlights the potential of TpDa-COF@Py + hv as a promising strategy to enhance phototheronostics and achieve effective tumor regression. Accordingly, the study supplies a generalized 1 O 2 "afterglow" nanoplatform to improve the effectiveness of PDT.

光动力疗法（PDT）是一种新兴的治疗方法，但常常受到氧气供应的限制。通过分级生成来延长单线态氧（ 1 O 2 ）的寿命是提高PDT疗效的有效方法。在此，合成了一种基于亚胺的纳米级COF（TpDa-COF），并用吡啶酮衍生结构（Py）进行功能化，以创建一个存储1 O 2 的纳米平台TpDa-COF@Py，它可以可逆地捕获和释放1 O 2 。在 660 nm 激光照射下，Py 与 COF 主链中卟啉基序产生的 1 O 2 相互作用，生成富含 1 O 2 的 COF (TpDa-COF@Py + hv)，然后在生理温度下通过逆狄尔斯-阿尔德反应释放 1 O 2 。激光照射时连续产生和释放 1 O 2 会产生“余辉”效应并延长 1 O 2 寿命。体外细胞毒性测定表明，TpDa-COF@Py + hv 对 4T1 细胞表现出极低的半数抑制浓度 (IC 50 )，仅为 0.54 µg/mL。值得注意的是，与单独的 TpDa-COF 相比，Py 介导的 TpDa-COF@Py 纳米平台在激光照射下表现出增强的细胞杀伤能力，这归因于持续的 1 O 2 循环。进一步的体内评估凸显了 TpDa-COF@Py + hv 作为增强光热治疗和实现有效肿瘤消退的有前途策略的潜力。因此，该研究提供了通用的 1 O 2 “余辉”纳米平台来提高 PDT 的有效性。