Lighting-Up tumor for assisting resection via spraying NIR fluorescent probe of γ-glutamyltranspeptidas

Abstract

For the precision resection, development of near-infrared (NIR) fluorescent probe based on specificity identification tumor-associated enzyme for lighting-up the tumor area, is urgent in the field of diagnosis and treatment. Overexpression of γ-glutamyltranspeptidase, one of the cell-membrane enzymes, known as a biomarker is concerned with the growth and progression of ovarian, liver, colon and breast cancer compared to normal tissue. In this work, a remarkable enzyme-activated NIR fluorescent probe NIR-SN-GGT was proposed and synthesized including two moieties: a NIR dicyanoisophorone core as signal reporter unit; γ-glutamyl group as the specificity identification site. In the presence of γ-GGT, probe NIR-SN-GGT was transformed into NIR-SN-NH2, the recovery of Intramolecular Charge Transfer (ICT), liberating the NIR fluorescence signal, which was firstly employed to distinguish tumor tissue and normal tissues via simple "spraying" manner, greatly promoting the possibility of precise excision. Furthermore, combined with magnetic resonance imaging by T2 weight mode, tumor transplanted BABL/c mice could be also lit up for first time by NIR fluorescence probe having a large stokes, which demonstrated that probe NIR-SN-GGT would be a useful tool for assisting surgeon to diagnose and remove tumor in clinical practice.