Glutathione-Triggered “Off–On” Release of Anticancer Drugs from Dendrimer-Encapsulated Gold Nanoparticles

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 an...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2013-07, Vol.135 (26), p.9805-9810
Main Authors: Wang, Xinyu, Cai, Xiaopan, Hu, Jingjing, Shao, Naimin, Wang, Fei, Zhang, Qiang, Xiao, Jianru, Cheng, Yiyun
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Cell Survival - drug effects
Dendrimers - chemistry
Dose-Response Relationship, Drug
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Carriers - chemistry
Drug Screening Assays, Antitumor
Glutathione - chemistry
Gold - chemistry
HeLa Cells
Humans
Metal Nanoparticles - chemistry
Molecular Structure
Structure-Activity Relationship
Sulfhydryl Compounds - chemistry
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Summary: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.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja402903h