title: Glutathione-triggered "off-on" release of anticancer drugs from dendrimer-encapsulated gold nanoparticles.
abstract: Polymeric nanoparticles that can stably load anticancer drugs and release them in response to a specific trigger such as glutathione are of great interest in cancer therapy. In the present study, dendrimer-encapsulated gold nanoparticles (DEGNPs) were synthesized and used as carriers of thiolated anticancer drugs. Thiol-containing drugs such as captopril and 6-mercaptopurine loaded within DEGNPs showed an "Off-On" release behavior in the presence of thiol-reducing agents such as glutathione and dithiothreitol. Thiolated doxorubicin and cisplatin, loaded within the nanoparticle, showed much reduced cytotoxicity as compared to the free anticancer compounds. The toxicity of drug-loaded DEGNPs can be enhanced by improving the intracellular glutathione. Glutathione-triggered release of thiolated doxorubicin within cancer cells is further confirmed by flow cytometry and confocal laser scan microscopy studies. In addition, DEGNPs showed excellent biocompatibility on several cell lines. This study provides a new insight into biomedical applications of dendrimers and dendrimer-encapsulated nanoparticles.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200062, P.R. China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Cai
authors.forename: Jingjing
authors.initials: J
authors.lastname: Hu
authors.forename: Naimin
authors.initials: N
authors.lastname: Shao
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jianru
authors.initials: J
authors.lastname: Xiao
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D013438:Sulfhydryl Compounds; D006046:Gold; D004317:Doxorubicin; D005978:Glutathione