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 (¹O₂) 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 ¹O₂-storing nanoplatform TpDa-COF@Py, which can reversibly capture and release ¹O₂. Under 660 nm laser exposure, Py interacts with ¹O₂ produced by the porphyrin motif in COF backbones to generate ¹O₂-enriched COF (TpDa-COF@Py + hv), followed by the release of ¹O₂ through retro-Diels-Alder reactions at physiological temperatures. The continuous producing and releasing of ¹O₂ upon laser exposure leads to an "afterglow" effect and a prolonged ¹O₂ lifespan. In vitro cytotoxicity assays demonstrates that TpDa-COF@Py + hv exhibits an extremely low half-maximal inhibitory concentration (IC₅₀) 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 ¹O₂ 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 ¹O₂ "afterglow" nanoplatform to improve the effectiveness of PDT.