Development of a hypoxia-activated red-emission fluorescent probe for in vivo tumor microenvironment imaging and anti-tumor therapy

Abstract

Hypoxia, a significant feature of the tumor microenvironment, is closely associated with tumor growth, metastasis, and drug resistance. In the field of tumor microenvironment analysis, accurately imaging and quantifying hypoxia - a critical factor associated with tumor progression, metastasis, and resistance to therapy - remains a significant challenge. Herein, a hypoxia-activated red-emission fluorescent probe, ODP, for in vivo imaging of hypoxia in the tumor microenvironment is presented. Among various imaging methods, optical imaging is particularly convenient due to its rapid response and high sensitivity. The ODP probe specifically targets nitroreductase (AzoR), an enzyme highly expressed in hypoxic cells, playing a vital role by catalyzing the cleavage of azo bonds. The optical properties of ODP exhibited excellent performance in terms of fluorescence enhancement, fluorescence lifetime (0.81 ns), and detection limit (0.86 µM) in response to SDT. Cell imaging experiments showed that ODP could effectively detect and image intracellular hypoxia and the imaging capability of ODP was studied under various conditions including cell migration, antioxidant treatment, and different incubation times. Through comprehensive in vitro and in vivo experiments, including cellular imaging and mouse tumor models, this work demonstrates the efficacy of ODP in accurately detecting and imaging hypoxia. Moreover, ODP's potential in inducing apoptosis in cancer cells offers a promising avenue for integrating diagnostic and therapeutic strategies in cancer treatment. This innovative approach not only contributes to the understanding and assessment of tumor hypoxia but also opens new possibilities for targeted cancer therapy.

Keywords: Fluorescent probe; Imaging hypoxia; In vivo imaging; Inducing apoptosis; Tracking tumor dynamics.