Design of a multifunctional biotinylated copper complex for visualization and quantification of cancer hypoxia levels

Abstract

Hypoxia, a typical hallmark of solid tumors, is associated closely with tumor progression and therapy resistance. Optical imaging has served as a powerful approach to study hypoxia in cancer cells. However, the noninvasive quantification of hypoxia levels in cancer cells is currently lacking. Herein, we report the design, synthesis, and biological evaluation of compound M, a novel fluorescence chemosensor to quantify hypoxia levels that relies on hypoxia-activated bioreduction. The remarkable selectivity and spectrum stability of compound M enabled us to visualize hypoxia and quantify the degree of hypoxia by high-throughput flow cytometry analysis in oxygen-deprived cancer cells. Furthermore, the HIF-1α level suppression in cancer cells was achieved by compound M. With the realization of hypoxia levels quantification in a cobalt-treated hypoxia model, we envision that multifunctional compound M will find widespread applications in the study of physiological and pathological processes associated with hypoxia.