A mitochondria-targeted and viscosity-sensitive near-infrared fluorescent probe for visualization of fatty liver, inflammation and photodynamic cancer therapy

Abstract

Elucidating the intrinsic relationship between disease and mitochondrial viscosity is great significance for understanding the diagnosis and treatment of fatty liver, inflammation and cancer. However, the development of a single mitochondrial viscosity fluorescent probe capable of visualizing multiple disease models and achieving photodynamic cancer therapy function is severely deficient and remains a great challenge. Herein we intelligently designed a mitochondria-targeted and viscosity-sensitive near-infrared (NIR) fluorescent probe POTA-OH, containing a p-hydroxydiphenylamino substituted oxanthracene moiety as the strong electron donor (D), a pyridinium cationic unit as the electron acceptor (A) and the mitochondria-targeted group. With increasing the viscosity level, POTA-OH displayed a significant “turn-on” fluorescence behavior at 720 nm, and an excellent linear relationship with viscosity from 0.89 cP to 945 cP. Meanwhile, POTA-OH could achieve effective reactive oxygen species production upon a 635 nm red laser irradiation. Using POTA-OH, we have demonstrated the visualization of fatty liver tissues, inflammation living mice, tumor living mice and even clinic cancer patient tissues samples via mitochondrial viscosity imaging. Furthermore, we revealed that POTA-OH has the potential of simultaneous PDT treatment in vitro and immediate evaluation of its therapeutic effect. Importantly, high-efficient PDT of POTA-OH has also successfully achieved for in vivo PDT antitumor, making it a promising integrated reagent for cancer diagnosis, treatment and even evaluation of PDT efficacy.