Photodriven Nanopump with Self-Augmented ROS Generation and Controllable Drug Release for Precisely Tuning Tumor Photodynamic-Chemotherapy

Although the stimulus-responsive nanoplatform shows excellent drug delivery preponderance in controlling drug release, its application is still inevitably restricted by exogenous uncontrollability, scarce biocompatibility, and a complex tumor microenvironment. Here, a photodriven self-augmented precision controllable nanoplatform was constructed by designing a novel pump-type switch cross-linker with 1 O 2 -activation to covalently cross-link the topoisomerase I of 7-ethyl-10-hydroxycamptothecin (SN38) concurrently loading chlorin e6 (Ce6) to obtain the anticipative nanopump-CNs. After laser irradiation, the nanopump can be controllably unlocked, realizing the self-enhanced cascade amplification process of producing reactive oxygen species (ROS) while releasing the chemotherapy drug. Significantly, SN38 can effectively increase the sensitivity of tumor-related organelles to ROS while inducing DNA damage in tumor cells, thus, amplifying the efficacy of photodynamics caused by Ce6. This cascade self-enhanced drug nanosystem based on exogenous controlled chemotherapy and photodynamic therapy is expected to provide a new perspective for designing nanomedicine with a precise regulation model for malignant tumor therapy.