AIEgen-Based Photoactivatable Polymeric Prodrug Nanoplatform for Combined Photodynamic-Chemotherapy

The combination of photodynamic therapy (PDT) and chemotherapy is an innovative cancer treatment strategy, but its clinical application faces challenges: (1) conventional photosensitizers exhibit fluorescence quenching and reduced ROS generation due to aggregation in aqueous environments, and (2) existing nanocarriers suffer from low drug loading efficiency, premature leakage, and systemic toxicity. To overcome these issues, we developed a photoactivatable codelivery system integrating a red-emissive AIEgen photosensitizer (BTPTT-NTPE, BC) with a ROS-responsive polymeric paclitaxel (PTX) prodrug. Harnessing the AIE effect, the AIEgen photosensitizer in its aggregated state within the codelivery system not only resolves the fluorescence quenching issue common to conventional photosensitizers but also demonstrates exceptional photostability and efficient ROS generation. The BC@PTP prodrug achieves a high PTX loading (18.0%) and enables spatiotemporally controlled drug release via light-activated prodrug cleavage. This multifunctional system demonstrates remarkable antitumor efficacy through synergistic PDT-chemotherapy effects in a HeLa-bearing mouse animal model.