A hemicyanine-based fluorescence probe for selective detection of CYP2D6 in living cells and tumor-bearing mice

Abstract

Cytochrome P450 (CYP) 2D6, as the only active CYP2D subfamily enzyme in humans, involved in metabolizing 25% of clinical drugs, including antidepressants, antiarrhythmic drugs, antipsychotics and analgesics. Herein, two novel enzyme-activatable fluorescent probes (McMe and BnMcMe) were constructed and synthesized to monitor the activity of CytochromeP4502D6 (CYP2D6) in complex biological systems. McMe possessed excellent selectivity and sensitivity in response to CYP2D6 enzyme with 9-fold fluorescence changes and the limit of detection (LOD) = 0.052 nM. The fruitful application of McMe in living cells and tumor-bearing mice implied that it can be used to measure the activity of endogenous CYP2D6. These researches indicated that McMe could be served as an effective molecular tool to specifically bio-image the activity of endogenous CYP2D6 in nude mice, which may provide assistance to investigate the function of CYP2D6 in drug metabolism and pathologic process.