Mitochondria-Targetable Near-Infrared Fluorescent Probe for Visualization of Hydrogen Peroxide in Lung Injury, Liver Injury, and Tumor Models

Abstract

Hydrogen peroxide (H₂O₂) overexpressed in mitochondria has been regarded as a key biomarker in the pathological processes of various diseases. However, there is currently a lack of suitable mitochondria-targetable near-infrared (NIR) probes for the visualization of H₂O₂ in multiple diseases, such as PM_2.5 exposure-induced lung injury, hepatic ischemia-reperfusion injury (HIRI), nonalcoholic fatty liver (NAFL), hepatic fibrosis (HF), and malignant tumor tissues containing clinical cancer patient samples. Herein, we conceived a novel NIR fluorescent probe (HCy-H₂O₂) by introducing pentafluorobenzenesulfonyl as a H₂O₂ sensing unit into the NIR hemicyanine platform. HCy-H₂O₂ exhibits good sensitivity and selectivity toward H₂O₂, accompanied by a remarkable "turn-on" fluorescence signal at 720 nm. Meanwhile, HCy-H₂O₂ has stable mitochondria-targetable ability and permits monitoring of the up-generated H₂O₂ level during mitophagy. Furthermore, using HCy-H₂O₂, we have successfully observed an overproduced mitochondrial H₂O₂ in ambient PM_2.5 exposure-induced lung injury, HIRI, NAFL, and HF models through NIR fluorescence imaging. Significantly, the visualization of H₂O₂ has been achieved in both tumor-bear mice as well as surgical specimens of cancer patients, making HCy-H₂O₂ a promising tool for cancer diagnosis and imaging-guided surgery.