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.