An ultra-stable bio-inspired bacteriochlorin analogue for hypoxia-tolerant photodynamic therapy

Abstract

Photodynamic therapy (PDT) greatly suffers from the weak NIR-absorption, oxygen dependence and poor stability of photosensitizers (PSs). Herein, inspired by natural bacteriochlorin, we develop a bacteriochlorin analogue, tetrafluorophenyl bacteriochlorin (FBC), by one-step reduction of tetrafluorophenyl porphyrin (TFPP).FBCcan realize deep tissue penetration, benefitting from the strong NIR absorption. The reactive oxygen species (ROS) generation capacity ofFBCcan retain around 60% with a 1.0 cm-thick pork skin as the barrier. Besides,FBCcould not only produce oxygen-dependent1O2, but also generate less oxygen-dependent O2−˙ and ˙OH to achieve excellent PDT even in hypoxic tumors. Moreover,FBCexhibits an ultra-high stability and it is almost unchanged even under visible light at room temperature for 15 months. Interestingly, the high reactivity of the fluorophenyl group makes it easy forFBCto produceFBCderivatives. A biocompatibleFBCnanogel could be directly formed by blendingFBCwith SH-PEG-SH. TheFBCnanogel displays excellent photodynamic efficacyin vitroandin vivo. Thus,FBCwould be a promising PS for the clinical PDT of deep tumors.