AIEgen Photosensitizer-Loaded Silica Nanoparticles for Lysosomes-Targeting Photodynamic Therapy in Tumor

Aggregation-induced emission (AIE)-based photosensitizers (PSs) are well-known for their exceptional biocompatibility and high irradiation-induced reactive oxygen species (ROS) generation capacity, making them promising candidates for photodynamic therapy (PDT). In antitumor treatment, enhancing the spatiotemporal specificity of AIEgen PSs can maximize the efficacy of suppressing tumor cells. Lysosomes, as digestive cellular organelles, can be perturbed by various external stimuli, leading to cellular dysfunction and even apoptosis. This makes them ideal targets for effective and precise PDT. In this study, an AIE photosensitizer MEO-TTMN (MT) was encapsulated with a silica shell to develop AIE-based silica nanoparticles (NPs), MT@SiO2-MP NPs, for antitumor PDT. The absorption and emission peaks of these NPs were at 513 and 675 nm, respectively. Upon irradiation, MT@SiO2-MP NPs exhibited a stronger ROS generation capacity when compared with the commercial photosensitizer chlorin e6 (Ce6). The decoration of the morpholine group on the surface of the silica shell facilitated MT@SiO2-MP NPs to accumulate specifically in the cellular lysosomes. A high level of ROS was proven to be in situ generated at the lysosomal sites by irradiation, which led to the damage of lysosomes and subsequent apoptosis of tumor cells. The in vivo PDT of tumor-bearing mouse demonstrated that MT@SiO2-MP NPs significantly suppressed the growth of the tumor. This work has provided efficient lysosome-targeting NPs to improve PDT efficacy and accuracy, which is beneficial for cancer therapy in the field of nanomedicine research.