Size Optimization of Organic Nanoparticles with Aggregation‐Induced Emission Characteristics for Improved ROS Generation and Photodynamic Cancer Cell Ablation

Abstract Aggregation‐induced emission (AIE) fluorogens provide new opportunities to promote efficient reactive oxygen species (ROS) production in aggregates, which represent the promising candidates to construct theranostic nanoparticles for photodynamic therapy (PDT), but the size effect has been rarely explored. Herein, a universal method to fabricate organic nanoparticles with controllable sizes is reported and it demonstrates that ≈45 nm is the optimal size of AIE nanoparticles for PDT. Different from conventional Ce6 nanoparticles which show largely reduced fluorescence and ROS generation with increasing nanoparticle size, AIE nanoparticles show gradually enhanced brightness and ROS generation upon increasing the sizes from 6 to ≈45 nm. Further increasing sizes could continue to intensify the nanoparticle's brightness at the expense of ROS production, with the optimal size for ROS generation being achieved at ≈45 nm. Both 2D monolayer cell and 3D multicellular spheroid experiments confirm that 45 nm AIE nanoparticles have the highest cellular uptake, the deepest penetration depth, and the best photodynamic killing effect. Such a study not only manifests the advantages of AIE photosensitizers, but also delivers the optimal size ranging for efficient PDT, which shall provide an attractive paradigm to guide the development of phototheranostic nanoparticles besides molecular design to further promote PDT applications.