Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition

doi:10.1021/jacs.9b03503

	Enhanced Tumor-Specific Disulfiram Chemotherapy by In Situ Cu2+ Chelation-Initiated Nontoxicity-to-Toxicity Transition
	Wu, Wencheng 1,2; Yu, Luodan 1,2; Jiang, Quzi 1,2; Huo, Minfeng 1,2; Lin, Han 1,2; Wang, Liying1,3 ; Chen, Yu 1; Shi, Jianlin 1
	2019-07-24
发表期刊	JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (IF:14.4[JCR-2023],14.8[5-Year])
ISSN	0002-7863
卷号	141 期号:29 页码:11531-11539
发表状态	已发表
DOI	10.1021/jacs.9b03503
摘要	The 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.
收录类别	SCI ; SCIE ; EI
语种	英语
资助项目	Shanghai Sailing Program[19YF1453700]
WOS研究方向	Chemistry
WOS类目	Chemistry, Multidisciplinary
WOS记录号	WOS:000477787400029
出版者	AMER CHEMICAL SOC
EI主题词	Biodegradation ; Chelation ; Chemotherapy ; Controlled drug delivery ; Copper ; Drug products ; Ions ; Nanoparticles ; Oxidation ; Silica ; Silica nanoparticles ; Targeted drug delivery ; Toxicity ; Tumors
WOS关键词	CANCER ; DRUG ; NANOPARTICLES ; COPPER(II) ; PROTEASOME ; MANGANESE ; STRATEGY ; HYPOXIA ; PH
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/61136
专题	物质科学与技术学院_博士生
通讯作者	Yu, Luodan; Shi, Jianlin
作者单位	1.Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai 200050, Peoples R China 2.Univ Chinese Acad Sci, Ctr Mat Sci & Optoelect Engn, Beijing 100049, Peoples R China 3.ShanghaiTech Univ, Sch Phys Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式 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):11531-11539.
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),11531-11539.
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):11531-11539.