Chlorine Radical‐Driven, Oxygen‐Independent Afterglow Nanoplatform for Tumor Microenvironment—Adaptive Imaging and Therapy

Persistent luminescence (afterglow) imaging offers exceptional signal-to-background ratios by eliminating tissue autofluorescence, yet most organic systems depend on oxygen-mediated reactive oxygen species and fail in hypoxic environments such as solid tumors. Herein, we report an oxygen-independent afterglow mechanism driven by chlorine radicals (·Cl). Hemicyanine-centered nanoparticles (Hcy@AgCl-PEG) were prepared by nanoprecipitation, surface-decorated with AgCl heterostructures for light-activated ·Cl generation, and stabilized with methoxypolyethylene glycol. Upon irradiation, AgCl produces ·Cl, which adds across the dye's conjugated double bond to form metastable epoxide intermediates; subsequent epoxide decomposition releases stored chemical energy, re-exciting the dye and yielding intense afterglow emission regardless of O₂ concentration. This strategy extends to cyanine and porphyrin fluorophores, underscoring its generality. A pH-responsive variant (Hcy-pH@AgCl) further enables afterglow imaging of pH-responsive. In vivo, Hcy@AgCl-PEG achieves high-contrast tumor imaging and leverages the oxidative potency of ·Cl to induce pronounced photodynamic therapy via oxidative stress and DNA single-electron oxidation. Together, these findings establish a new paradigm for oxygen-free afterglow systems and deliver a versatile theranostic platform for imaging and treatment in dynamic, hypoxia-associated pathologies.