A mitochondrial targeted fluorescent probe for imaging nitroreductase activity and photodynamic therapy in tumor cells.

Abstract

The hypoxic environment in tumors is closely linked to tumor structure, function, dissemination, invasion, metastasis, and drug resistance. Nitroreductase (NTR) is often recognized as a biomarker to evaluate the hypoxia degree for tumor cells. Traditional detection methods such as PET, MRI and multispectral photoacoustic tomography have limitations. Fluorescent probes have garnered attention due to their high sensitivity, rapid response, specificity, and non-invasive nature. In this study, we introduced a novel small molecule fluorescent probe, T-TPE-NO₂, designed with an AIE molecular framework TPE and successfully targeted to the mitochondria of tumor cells. The probe had high selectivity and could detect NTR activity in a broad pH range. Additionally, the probe exhibits high sensitivity with a LOD of 46.3 ng/mL. Under tumor NTR, the probe emitted strong fluorescence signals and generated a substantial amount of reactive oxygen species upon laser irradiation, thereby inducing tumor cell death and enabling photodynamic therapy. The synthesis, structural and morphological characterization of the probe were rigorously validated. Experimental results demonstrate that T-TPE-NO₂ exhibited high sensitivity and selectivity for tumor cells, highlighting its potential application in photodynamic therapy. This research offers a new approach for the detection and treatment of tumor hypoxia.