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.

Gold nanoparticles explore cells: Cellular uptake and their use as intracellular probes

“…SERS has been extensively applied in biomedical applications often for label-free detection of biomolecules in cells and tissues [4,22]. AuNPs have been used as intracellular probes for SERS [23] to monitor release of drugs inside cells [24] as well as to probe molecules by targeting them to cellular compartments such as mitochondria, endosomes and the cell nucleus [11,22,25,26]. The key for utilisation of nanoparticles inside cells for SERS and other measurements is their mechanism of uptake.…”

Inorganic Nanocarriers Overcoming Multidrug Resistance for Cancer Theranostics

“…The surface of gold nanoparticles could be easily modified with several high affinity functional groups to carry bioactive compounds or for PEGylation. Besides, gold nanoparticles have been widely applied for imaging, such as for CT imaging owing with their high atomic number and electron density, for optical imaging with high optimal light scattering performances,95 for photoacoustic (PA) imaging with the produced thermal after laser irradiation,96 and for Raman spectroscopy (SERS) imaging with the enhanced scattering on their surface 97…”

Scanning angle Raman spectroscopy: Investigation of Raman scatter enhancement techniques for chemical analysis

“…545 Monitoring 6-mercaptopurine and 6-thioguanine was performed with SERS in real time with drug detection limits in the nM regime. These studies demonstrate SERS ability to chemically target and track species in complex environments.…”