Disulfiram Copper Nanoparticles Prepared with a Stabilized Metal Ion Ligand Complex Method for Treating Drug-Resistant Prostate Cancers

doi:10.1021/acsami.8b14940

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	Disulfiram Copper Nanoparticles Prepared with a Stabilized Metal Ion Ligand Complex Method for Treating Drug-Resistant Prostate Cancers
	Chen, Wu 1; Yang, Wen 2; Chen, Pengyu 2; Huang, Yongzhuo3 ; Li, Feng 1
刊名	ACS APPLIED MATERIALS & INTERFACES
	2018-12-05
卷号	10 期号:48 页码:41118-41128
关键词	disulfiram copper diethyldithiocarbamate drug resistance prostate cancer nanoparticle drug delivery paraptosis
ISSN号	1944-8244
DOI	10.1021/acsami.8b14940
文献子类	Article
英文摘要	Disulfiram (DSF), an alcohol-aversion drug, has been explored for cancer treatment. Copper diethyldithiocarbamate (Cu(DDC)(2)) complex formed by DSF and copper ions is a major active ingredient for its anticancer activity. Direct administration of Cu(DDC)(2) is a promising strategy to enhance the anticancer efficacy of DSF. However, efficient drug delivery remains a significant challenge for Cu(DDC)(2) and hinders its clinical use. In this study, we developed a facile stabilized metal ion ligand complex (SMILE) method to prepare Cu(DDC)(2) nanoparticles (NPs). The SMILE method could prepare Cu(DDC)(2) NPs with different types of stabilizers including 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine poly(ethylene glycol) (PEG) 2000, D-alpha-tocopherol PEG 1000 succinate, methoxy PEG 5000-b-poly(L-lactide) 5000, and other generally recognized as safe excipients approved by the US Food and Drug Administration. The optimized formulations demonstrated excellent drug-loading efficiency (close to 100%), high drug concentrations (increased drug concentration by over 200-fold compared to the traditional micelle formulation), and an optimal particle size in the sub-100 nm range. Cu(DDC)(2) NPs exhibited outstanding stability in serum for 72 h and can also be stored at room temperature for at least 1 month. The anticancer effects of Cu(DDC)(2) NP formulations were determined by multiple assays including 3-(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl tetrazolium bromide assay, colony-forming assay, calcein-AM/propidium iodide staining, and others. Cu(DDC)(2) NPs showed excellent activity against drug-resistant prostate cancer cells and other cancer cells with a half-maximal inhibitory concentration (IC50) of around 100 nM. Our study also demonstrated that Cu(DDC)(2) NPs induced cell death in drug-resistant prostate cancer cells (DU145-TXR) through paraptosis, which is a nonapoptotic cell death. To our best knowledge, the SMILE method provides, for the first time, a simple yet efficient process for generating Cu(DDC)(2) NPs with high drug concentration, excellent loading efficiency, and desirable physicochemical properties. This method could potentially address drug delivery challenges of DSF/copper-based chemotherapy and facilitate its clinical translation.
资助项目	Auburn University startup fund[00000000] ; National Science Foundation[CBET-1701363]
WOS关键词	TARGETS CANCER ; CELL-DEATH ; IN-VITRO ; DELIVERY ; DIETHYLDITHIOCARBAMATE ; FORMULATION ; APOPTOSIS ; REVERSES ; THERAPY ; STRESS
WOS研究方向	Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000452694100019
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279471]
专题	药物制剂研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Huang, Yongzhuo; Li, Feng
作者单位	1.Auburn Univ, Harrison Sch Pharm, Dept Drug Discovery & Dev, Auburn, AL 36849 USA; 2.Auburn Univ, Mat Res & Educ Ctr, Mat Engn, Dept Mech Engn, Auburn, AL 36849 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Wu,Yang, Wen,Chen, Pengyu,et al. Disulfiram Copper Nanoparticles Prepared with a Stabilized Metal Ion Ligand Complex Method for Treating Drug-Resistant Prostate Cancers[J]. ACS APPLIED MATERIALS & INTERFACES,2018,10(48):41118-41128.
APA	Chen, Wu,Yang, Wen,Chen, Pengyu,Huang, Yongzhuo,&Li, Feng.(2018).Disulfiram Copper Nanoparticles Prepared with a Stabilized Metal Ion Ligand Complex Method for Treating Drug-Resistant Prostate Cancers.ACS APPLIED MATERIALS & INTERFACES,10(48),41118-41128.
MLA	Chen, Wu,et al."Disulfiram Copper Nanoparticles Prepared with a Stabilized Metal Ion Ligand Complex Method for Treating Drug-Resistant Prostate Cancers".ACS APPLIED MATERIALS & INTERFACES 10.48(2018):41118-41128.