title: Label-free Raman spectroscopy for accessing intracellular anticancer drug release on gold nanoparticles.
abstract: We investigated glutathione (GSH)-induced purine or pyrimidine anticancer drug release on gold nanoparticle (AuNP) surfaces by means of label-free Raman spectroscopy. GSH-triggered releases of 6-thioguanine (6TG), gemcitabine (GEM), acycloguanosine (ACY), and fadrozole (FAD) were examined in a comparative way by means of surface-enhanced Raman scattering (SERS). The GSH-induced dissociation constant of GEM (or ACY/FAD) from AuNPs was estimated to be larger by more than 38 times than that of 6TG from the kinetic relationship. Tripeptide control experiments were presented to check the turn-off Raman signalling mechanism. Dark-field microscopy (DFM) and transmission electron microscopy (TEM) indicated the intracellular AuNP loads. After their cellular uptake, GEM, ACY, and FAD would not show SERS intensities as strong as 6TG. This may be due to easier release of GEM, ACY, and FAD than 6TG by intracellular reducing species including GSH. We observed fairly strong SERS signals of GEM and 6TG in cell culture media solution. Our CCK-8 cytotoxicity assay data support that 6TG-AuNPs did not exhibit a substantial decrease in cell viability presumably due to strong binding. Label-free confocal Raman spectroscopy can be utilized as an effective tool to access intracellular anticancer drug release.
authors.affiliation: Department of Chemistry, Soongsil University, Seoul, 156-743, Korea.
authors.forename: Kwang-Su
authors.initials: KS
authors.lastname: Ock
authors.forename: Erdene Ochir
authors.initials: EO
authors.lastname: Ganbold
authors.forename: Jin
authors.initials: J
authors.lastname: Park
authors.forename: Keunchang
authors.initials: K
authors.lastname: Cho
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Joo
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006046:Gold / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013866:Thioguanine / Q000378:metabolism / Q000494:pharmacology; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D006046:Gold; D013866:Thioguanine; D005978:Glutathione; D000093542:Gemcitabine