pH-responsive AIE nanogels for synergistic chemo-photodynamic cancer therapy with imaging guidance

Abstract Photodynamic therapy (PDT) is a promising cancer treatment that uses photosensitizers (PSs) to generate cytotoxic reactive oxygen species (ROS) under light, but improving its efficacy is crucial for clinical applications. To address this, we propose a smart nanoplatform (P@BAO-DOX) for synergistic chemo-photodynamic therapy, featuring efficient PDT, controllable drug release, and fluorescence imaging guidance. We designed an aggregation-induced emission (AIE)-based PS (BAO) with effective ROS generation and NIR-II fluorescence. Additionally, BAO as a PS and doxorubicin (DOX) as a chemo drug were encapsulated in pH-responsive nanogels (PNA) to obtain P@BAO-DOX nanogels. Upon uptake by tumor cells, the nanogel releases drugs in acidic conditions, leading to cell death. White light irradiation further triggers BAO to produce substantial ROS, enhancing phototoxicity and synergistic chemo-PDT cancer therapy. Thus, P@BAO-DOX nanogels, as a smart nanoplatform, offer precise drug release and efficient ROS generation for imaging-guided chemo-PDT synergistic therapy, showing promise in advancing cancer treatment.