A HClO-activated BODIPY based ratiometric fluorescent probe with dual near-infrared channels for differentiating cancerous cells from normal cells and surgical guidance of tumor resection

Abstract

Cancer (malignant tumor), a serious disease with a high mortality rate, early-stage diagnosis and treatment are very important for cancer therapy. The average concentration of reactive oxygen species (ROS) in cancer cells is ten times higher than in normal cells, and the overexpression of hypochlorous acid (HClO) is closely associated with cancer progression. Herein, a novel near-infrared (NIR) Golgi apparatus-targetable (GA) fluorescent probe GA-BOD-S was synthesized using the BODIPY and phenothiazine as the basic fluorescence framework for HClO monitoring. GA-BOD-S exhibited a colorimetric and ratiometric dual-mode recognition for HClO with the excellent merits including low detection limit (35 nM), fast response time (within 13 s), and exceptional GA targeting capability (Pearson's coefficient 0.98). Notably, both fluorescence emission wavelengths of GA-BOD-S before and after reaction with HClO are located in the NIR region, significantly enhancing the quality of fluorescence imaging in vivo. Cellular experiments revealed that GA-BOD-S can effectively visualize both endogenous and exogenous HClO within cells and living zebrafish. GA-BOD-S was successfully employed for high-contrast imaging of cancer cells and normal cells based on the differences in intracellular ROS levels, and achieved in-situ imaging of tumors in vivo. Furthermore, the precision of tumor resection surgery was significantly improved under the guidance of fluorescence probe GA-BOD-S, which provided a new perspective for the diagnosis and treatment of cancer disease.

Keywords: BODIPY; Golgi apparatus; Hypochlorous acid; Near-infrared fluorescent probe; Surgical guidance.