Ionic fluorescent sensor targeting receptor tyrosine kinases for biosystems imaging and application in flow cytometry

Abstract

Fluorescent imaging of receptor tyrosine kinases in living biosystems is an important means for the early diagnosis of cancer, herein an ionic fluorescent sensor (SNB) composed of targeting unit (sunitinib) and nile blue fluorophore linked via long flexible chain has been designed and evaluated. The SNB sensor exhibits distinct fluorescence responses to receptor tyrosine kinases derived from unfolding strategy and targeting ability, which were evaluated through 2D NMR analyses, optical studies, kinase activity assays. The SNB sensor has excellent membrane fluorescent imaging by electrostatic adsorption and can selectively insert into receptor tyrosine kinases domain pocket on the membrane of cancer cell lines. The SNB sensor has been successfully applied in flow cytometry for cell sorting and fluorescence imaging with tumor mouse model in vivo. The SNB senor may help transition the technology into a widely suitable tool for flow cytometry, imaging with confocal microscopes, whole animal imaging and possibly facilitating early diagnoses and treatment of cancer.