Hydrazide D-luciferin for in vitro selective detection and intratumoral imaging of Cu2+

Copper is an essential micronutrient involved in fundamental life processes but using a bioluminescence (BL) probe to selectively sense Cu2+ in vitro or image Cu2+ in vivo is still unavailable. Herein, a latent BL probe hydrazide D-luciferin (1) was rationally designed and successfully applied it for selective detection of Cu2+ in vitro and imaging Cu2+ in living cells and in tumors. Upon the catalysis of Cu2+, 1 was converted to D-luciferin and turned on the BL in the presence of firefly luciferase (fLuc). In vitro tests indicated that 1 could be applied for highly selective sensing Cu2+ within the range of 0-80 mu M with a limit of detection (LOD) of 39.0 nM. Cell and animal experiments indicated that 1 could be applied for specific BL imaging of Cu2+ in living cells and tumors and the BL signal of 1 was more stable and longer than that of D-luciferin. We envision that this unique probe 1 might serve as an elucidative tool for further exploration of the biological roles of Cu2+ in physiological and pathological processes in the near future. (C) 2016 Elsevier B.V. All rights reserved.