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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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