A Light‐Triggered J‐Aggregation‐Regulated Therapy Conversion: from Photodynamic/Photothermal Therapy to Long‐Lasting Chemodynamic Therapy for Effective Tumor Ablation

Abstract Reactive oxygen species (ROS) have become an effective tool for tumor treatment. The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) takes advantage of various ROS and enhances therapeutic effects. However, the activation of CDT usually occurs before PDT, which hinders the sustained maintenance of hydroxyl radicals (⋅OH) and reduces the treatment efficiency. Herein, we present a light‐triggered nano‐system based on molecular aggregation regulation for converting cancer therapy from PDT/photothermal therapy (PTT) to a long‐lasting CDT. The ordered J‐aggregation enhances the photodynamic properties of the cyanine moiety while simultaneously suppressing the chemodynamic capabilities of the copper‐porphyrin moiety. Upon light irradiation, Cu‐PCy JNPs demonstrate strong photodynamic and photothermal effects. Meanwhile, light triggers a rapid degradation of the cyanine backbone, leading to the destruction of the J‐aggregation. As a result, a long‐lasting CDT is sequentially activated, and the sustained generation of ⋅OH is observed for up to 48 hours, causing potent cellular oxidative stress and apoptosis. Due to their excellent tumor accumulation, Cu‐PCy JNPs exhibit effective in vivo tumor ablation through the converting therapy. This work provides a new approach for effectively prolonging the chemodynamic activity in ROS‐based cancer therapy.