A singlet oxygen-storing covalent organic framework for "Afterglow" photodynamic therapy.

An imine-based nanoscale COF has been synthesized and functionalized with a pyridone-derived structure to create a singlet oxygen-storing nanoplatform, which can continuously produce and release singlet oxygen to realize "afterglow" photodynamic therapy. [Display omitted] Photodynamic therapy (PDT) is an emerging treatment but often restricted by the availability of oxygen. Enhancing the lifespan of singlet oxygen (1O 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 1O 2 -storing nanoplatform TpDa-COF@Py, which can reversibly capture and release 1O 2. Under 660 nm laser exposure, Py interacts with 1O 2 produced by the porphyrin motif in COF backbones to generate 1O 2 -enriched COF (TpDa-COF@Py + hv), followed by the release of 1O 2 through retro -Diels-Alder reactions at physiological temperatures. The continuous producing and releasing of 1O 2 upon laser exposure leads to an "afterglow" effect and a prolonged 1O 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 1O 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 1O 2 "afterglow" nanoplatform to improve the effectiveness of PDT. [ABSTRACT FROM AUTHOR]