Well-tailored Photosensitizers with Boosted Type-I ROS Generation by Fluorination Strategy for Precise Near-infrared Fluorescence-guided Photodynamic Therapy

Developing organic type I photosensitizers (PSs) that generate less oxygen-dependent reactive oxygen species (ROS) has long been recognized to be an appealing yet significantly challenging task in the field of photodynamic therapy (PDT), owing to the high oxygen dependency of conventional PDT, which impairs its overall therapeutic efficacy, particularly in hypoxic solid tumors. Herein, a molecular fluorination strategy to finely regulate PSs with bright near-infrared (NIR) fluorescence and superior type I ROS generation ability was exploited. Benefited from the improved donor-acceptor interaction, promoted intersystem crossing process, and increased spin-orbit coupling (SOC) constant, the optimal TIBT-5F simultaneously exhibits broad absorption with a larger molar extinction coefficient in the visible-light region, bright NIR fluorescence emission and stronger type I ROS generation efficiency, making TIBT-5F a promising candidate for precise NIR fluorescence-guided PDT. The as-prepared TIBT-5F nanoparticles (NPs) can quickly accumulate in the tumor site, effectively produce both type II and type I ROS and prominently suppress the tumor growth under a safe white light irradiation (40 mW/cm 2 ) with minimized systemic toxicity. This study thus offers a new insight into constructing advanced type I PSs for precise fluorescence imaging-guided tumor theranostics.