Perfluorocarbon-Encapsulated Porphyrin-Lipid Nanoparticles as a Photoactive Pyroptosis Inducer for Cancer Therapy

Pyroptosis is a unique mode of programmed cell death extensively accepted to outperform apoptosis in inducing rapid cell IP: 2038 10920 On: Wed 03 May 2023 10:19:49 death and evoking potent immune responses for further inhibiting tumor progression, recurrence, and metastasis. There-Copyr ght American Scientific Publishers fore, developing a safe and efficient pyroptosis inducer of cancer clls is highly desired. In this study, a biocompatible Delivered by Ingenta amphiphilic tetraphenylporphyrin-lysophospholipid conjugate (PPNH2-PC) was synthesized and further self-assembled with perfluorooctyl bromide (PFOB), forming PFOB-encapsulated porphyrin-lipid nanoparticles (PFOB@PPNH2-PC NPs) with a narrow size distribution of about 64.1 nm. Compared with the PPNH2-PC NPs without PFOB, the PFOB@PPNH2- PC NPs exhibited higher reactive oxygen species (ROS)-generating capability under light irradiation and induced more cellular death. We found that PFOB@PPNH2-PC NPs induced approximately 12 times more pyroptosis bubbles than PPNH2-PC NPs after 5-min light irradiation. Further analysis showed that pyroptosis was induced via caspase 3-mediated gasdermin E cleavage. Hence, this PFOB-encapsulated lipid NP holds the potential for further development as a pho-toactivatable pyroptosis inducer for cancer therapy.