Fluorocarbon-driven photosensitizer assembly decodes energy conversion pathway for suppressing breast tumor

Abstract

Despite enlarging the clinical applicability of organic photosensitizers in photodynamic therapy (PDT), current nanoencapsulation technology prefers to improve photothermal conversion rather than photochemical conversion from photon energy to reactive oxygen species (ROS)-represented chemical energy. To address it, a fluorocarbon-driven IR780 assembly was constructed to unlock the photochemical conversion pathway for suppressing breast tumor. Systematic experiments and molecular dynamic simulations successfully validated the feasibility and structure characteristics of fluorocarbon-driven IR780 assembly, where fluorocarbon-contained molecules assisted IR780 to assemble into nanoparticles via the energy-driven process. The orderly IR780 configuration in this assembly suppressed photothermal-represented nonradiative relaxation and considerably elevated collisional energy transfer for ROS production. As well, fluorocarbon could bound and release oxygen for mitigating hypoxia and improving ROS production, which united with hyaluronic acid stabilizer-mediated active targeting and fluorocarbon-mediated endosomal escape to cooperatively support the high-efficient PDT. Moreover, these inspiring characteristics triggered robust immunogenicity associated with immunogenic cell death, which eventually repressed the growth and metastasis of breast cancers especially when combining with anti-PD-L1. This unprecedented source design based on PDT principle paves a general method to develop desirable phototheranostic nanoagents.