SIC OpenIR
Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition
Wu, Wencheng; Yu, Luodan; Jiang, Quzi; Huo, Minfeng; Lin, Han; Wang, Liying; Chen, Yu; Shi, Jianlin
2019-07-24
Source PublicationJOURNAL OF THE AMERICAN CHEMICAL SOCIETY
ISSN0002-7863
Volume141Issue:29Pages:11531
SubtypeArticle
AbstractThe antitumor activity of disulfiram (DSF), a traditional US Food and Drug Administration-approved drug for the treatment of "alcohol-dependence", is Cu2+-dependent, but the intrinsic anfractuous biodistribution of copper in the human body and copper toxicity induced by exogenous copper supply have severely hindered its in vivo application. Herein, we report an in situ Cu2+ chelation-enhanced DSF-based cancer chemotherapy technique, using a tumor-specific "nontoxicity-to-toxicity" transition strategy based on hollow mesoporous silica nanoparticles as the functional carrier. Cu2+-doped, DSF-loaded hollow mesoporous silica nanoparticles were constructed for the rapid release of Cu2+ ions induced by the mild acidic conditions of the tumor microenvironment. This resulted in the rapid biodegradation of the nanoparticles and accelerated DSF release once the particles were endocytosed into tumor cells. The resulting in situ chelation reaction between the coreleased Cu2+ ions and DSF generated toxic CuET products and concurrently, Fenton-like reactions between the generated Cu+ ions and the high levels of H2O2 resulted in the production of reactive oxygen species (ROS) in the acidic tumor microenvironment. Both in vitro cellular assays and in vivo tumor-xenograft experiments demonstrated the efficient Cu-enhanced and tumor-specific chemotherapeutic efficacy of DSF, with cocontributions from highly toxic CuET complexes and ROS generated within tumors. This work provides a conceptual advancement of nanoparticle-enabled "nontoxicity-to-toxicity" transformation in tumors, to achieving high chemotherapeutic efficacy and biosafety.
DOI10.1021/jacs.9b03503
Language英语
WOS Research AreaChemistry
PublisherAMER CHEMICAL SOC
Citation statistics
Cited Times:47[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.sic.ac.cn/handle/331005/26963
Collection中国科学院上海硅酸盐研究所
Recommended Citation
GB/T 7714
Wu, Wencheng,Yu, Luodan,Jiang, Quzi,et al. Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2019,141(29):11531.
APA Wu, Wencheng.,Yu, Luodan.,Jiang, Quzi.,Huo, Minfeng.,Lin, Han.,...&Shi, Jianlin.(2019).Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,141(29),11531.
MLA Wu, Wencheng,et al."Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 141.29(2019):11531.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Wu, Wencheng]'s Articles
[Yu, Luodan]'s Articles
[Jiang, Quzi]'s Articles
Baidu academic
Similar articles in Baidu academic
[Wu, Wencheng]'s Articles
[Yu, Luodan]'s Articles
[Jiang, Quzi]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Wu, Wencheng]'s Articles
[Yu, Luodan]'s Articles
[Jiang, Quzi]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.