Real-Time Monitoring of Glutathione-Triggered Thiopurine Anticancer Drug Release in Live Cells Investigated by Surface-Enhanced Raman Scattering

Abstract

We investigated in vitro and in vivo glutathione (GSH)-induced intracellular thiopurine anticancer drug release on gold nanoparticle (Au NP) surfaces by means of label-free confocal Raman spectroscopy. Direct monitoring of GSH-triggered release of 6-mercaptopurine (6MP) and 6-thioguanine (6TG) was achieved in real time. Live cell imaging technique provides a nanomolar range release of 6MP and 6TG from Au NP surfaces after the injection of external GSH. In vivo SERS spectra of 6TG were obtained from the subcutaneous sites in living mice after GSH treatment. GSH-triggered releases of Cy5-dye assembled on 6TG-capped Au NPs were also compared using independent fluorescence measurements. Our work demonstrates that the time-lapse Raman spectroscopic tools are useful for monitoring of the controlled release of thiopurine drug molecules in vitro and in vivo.