Reactive Oxygen Species Self-Sufficient Multifunctional Nanoplatform for Synergistic Chemo-Photodynamic Therapy with Red/Near-Infrared Dual-Imaging

Developing multifunctional nanoplatforms that combine controlled drug release, therapy, and real-time monitoring of intracellular distribution of therapeutic agents can provide a solution for practical precision cancer therapy. Herein, a daylight activatable and red to near-infrared (NIR) dual-imaging guided multifunctional anticancer nanoplatform based on diselenium-conjugated and aggregation-induced emission fluorogen (AIEgen)-cross-linked oligoethylenimine polymer loaded with cisplatin (Pt) and biscyclometalated iridium(III) (Ir(III)) complex (Pt&Ir@P NPs) is reported. Upon short-time daylight irradiation, the nanoplatform generates reactive oxygen species (ROS), which help them to escape from endo/lysosomes via enhanced lysosomal membrane permeability. Meanwhile, the chemotherapeutic drug cisplatin and the photosensitizer (PS) Ir(III) complex are released via breaking the ROS-labile diselenium bond. The released PS, together with AIEgen, respond to the continuous long-time daylight irradiation and produce more ROS, inducing photodynamic therapy (PDT) and damaging the nucleus. Along with PDT, selenium liberates cisplatin and exerts chemotherapy in the presence of endogenous spermine. In addition, the red/NIR emitting Ir(III) complex and the engineered AIEgen act as dual-imaging agents for real-time monitoring the distribution of PS and polymer. This daylight responsive multifunctional nanoplatform for efficient anticancer therapy and imaging could provide an intriguing strategy for developing theranostic antitumor platforms.