Optical monitoring and treatment of breast cancer by a tumor hypoxia-activated multi-functional fluorescent sensor

Breast cancer is one of the most common cancers and a leading cause of death in women. Caused by the rapid growth, tumors show marked areas of hypoxia that play an important role in cancer progression and metastasis. We developed a near-infrared multifunctional azo-derivative, L4OD, to target the hypoxic environment of tu-mors. The release of fluorescent signals and lead compounds following its reaction with cytochrome P450 reductase allowed simultaneous optical detection and inhibited breast cancer tumor growth. The specificity of L4OD for cytochrome P450 reductase was confirmed in vitro through its reactions with tin chloride and rat liver microsomes. In HepG2 cells pre-treated with different oxygen concentrations (1%, 10%, and 21%) for 12 h, the red fluorescent intensity in the cells gradually increased as the oxygen concentration decreased, showing that L4OD can be used to image cytochrome P450 reductase enrichment and to monitor the associated hypoxic environment in cells. Using a mouse tumor xenograft model, we used L4OD successfully for in situ optical detection and tumor suppression in hypoxic regions of breast cancer tumors, with a high inhibition rate of 45%. These results indicate the high performance of L4OD for monitoring and therapy of breast cancer and the po-tential for further clinical application.