Size Optimization of Aggregation‐Induced Emission Nanoparticles for Enhanced Tumor Photodynamic Therapy

ABSTRACT

Photosensitizers with aggregation‐induced emission (AIE) features ensure robust reactive oxygen species (ROS) generation in aggregates, which have greatly advanced photodynamic therapy (PDT). But the current research has been predominantly focused on molecular engineering, whereas nano‐formulation barely serves as a tool to improve their biocompatibility. Herein, we demonstrate that the size of AIE nanoparticles (NPs) affects both photophysical properties and biological fates of encapsulated photosensitizers, and NPs of ∼30 nm represent the optimal size for PDT applications. With TSIC NPs of 8, 30, and 100 nm as the example, we demonstrate that increasing NP sizes promotes fluorescence quantum yield at the expense of photothermal effect due to the more rigidified intraparticle microenvironment, while the ROS generation efficacy exhibits a first increasing and then decreasing trend due to competition with fluorescence and heat generation, reaching a maximum at NPs of ∼30 nm (TSIC‐30). When TSIC NPs of smaller sizes (TSIC‐8) exhibit the fast tumor accumulation and clearance with the lowest overall tumor enrichment that hampers the in vivo PDT effect, TSIC‐30 shows the best tumor accumulation and PDT antitumor performance. In contrast, the poor ROS generation of larger NPs (TSIC‐100) delivers suboptimal PDT performance despite their highest tumor accumulation and prolonged tumor retention. Our work provides new insights into the influence of NP sizes on the photophysical properties and biological effects for optimal PDT.