title: GSH-mediated photoactivity of pheophorbide a-conjugated heparin/gold nanoparticle for photodynamic therapy.
abstract: In this study, we developed a new photosensitizer (PS)-conjugated hybrid nanoparticle comprised of gold nanoparticle (AuNP) as an efficient energy quencher, polysaccharide heparin and a second generation PS, pheophorbide a (PhA) for PDT. The hybrid nanoparticles (PhA-H/AuNPs) with an average size of 40nm were prepared by surface coating of AuNPs with PhA conjugated heparins via gold-thiol interaction. The glutathione (GSH)-mediated switchable photoactivity of the PhA-H/AuNPs was observed by fluorescence quenching and dequenching behaviors in the absence and presence of GSH. The photoactivity was significantly suppressed in aqueous media, but instantaneously restored at the GSH-rich intracellular environment to generate a strong fluorescence signal together with active production of singlet oxygen species with light treatment. In vitro cell tests revealed marked phototoxicity and high intracellular uptake of PhA-H/AuNPs in contrast with free PhA. The PhA-H/AuNPs also exhibited a prolonged circulation characteristic, enhanced tumor specificity, and improved photodynamic therapeutic efficacy compared with free PhA in tumor-bearing mice. As a result, the PhA-H/AuNPs may serve as an effective smart nanomedicine platform for PDT and have great potential for the clinical treatment of various tumors.
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, Daejeon 305-764, Republic of Korea.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.lastname: Nurunnabi
authors.lastname: Nafiujjaman
authors.forename: Yong-Kyu
authors.initials: YK
authors.lastname: Lee
authors.forename: Kang Moo
authors.initials: KM
authors.lastname: Huh
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D005978:Glutathione / Q000008:administration & dosage*; D006046:Gold / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D006801:Humans; D008027:Light; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D017319:Photosensitizing Agents; D002734:Chlorophyll; D006046:Gold; D006493:Heparin; D005978:Glutathione; C032623:pheophorbide a
keywords: Glutathione (PubChem CID: 124886); Gold nanoparticle (PubChem CID: 23985); Heparin (PubChem CID: 772); Pheophorbide a (PubChem CID: 5323510); Photodynamic therapy; Switchable photoactivity