Sub-50 nm Porphyrin Nanoparticles by Nanoprecipitation for Enhanced Generation of Singlet Oxygen

Porphyrin is an excellent photosensitizer for generating singlet oxygen (SO) in photodynamic therapy, but the aggregation issue has long been reported to weaken its therapeutic efficacy in practical applications. To address this challenge, we here report the design and synthesis of a series of amphiphilic porphyrin-terminated poly( N -isopropylacrylamide), which can self-assemble into sub-50 nm porphyrin nanoparticles via the nanoprecipitation route. We demonstrated that the NP size could be easily tuned by adjusting the self-assembly conditions. Furthermore, compared with pure hydrophobic porphyrin NPs prepared using a similar method, the resulting NPs exhibited an enhanced SO generation rate. Notably, the SO generation rate showed an intriguing temperature dependence, highlighting the potential of these NPs to serve as photosensitizers in photodynamic therapy applications.