Silk Fibroin-Modified Disulfiram/Zinc Oxide Nanocomposites for pH Triggered Release of Zn2+ and Synergistic Antitumor Efficacy

doi:10.1021/acs.molpharmaceut.0c00604

科研成果详情

题名	Silk Fibroin-Modified Disulfiram/Zinc Oxide Nanocomposites for pH Triggered Release of Zn2+ and Synergistic Antitumor Efficacy
作者	Zhao, Ying-Zheng1,2; Lin, Meng-Ting 2,3; Lan, Qing-Hua 2; Zhai, Yuan-Yuan 2; Xu, He-Lin2; Xiao, Jian2; Kou, Longfa4; Yao, Qing2,5
发表日期	2020-10-05
发表期刊	MOLECULAR PHARMACEUTICS 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Disulfiram zinc oxide nanoparticles synergistic effect pH-sensitive drug delivery
其他关键词	ZNO NANOPARTICLES ; OXIDATIVE STRESS ; TARGETS CANCER ; DRUG ; CYTOTOXICITY ; PACLITAXEL ; RESISTANCE ; CELL
摘要	Disulfiram (DSF) is an FDA-approved anti-alcoholic drug that has recently proven to be effective in cancer treatment. However, the short half-life in the bloodstream and the metal ion-dependent antitumor activity significantly limited the further application of DSF in the clinical field. To this end, we constructed a silk fibroin modified disulfiram/zinc oxide nanocomposites (SF/DSF@ZnO) to solubilize and stabilize DSF, and, more importantly, achieve pH triggered Zn2+ release and subsequent synergistic antitumor activity. The prepared SF/DSF@ZnO nanocomposites were spherical and had a high drug loading. Triggered by the lysosomal pH, SF/DSF@ZnO could induce the rapid release of Zn2+ under the acidic conditions and caused nanoparticulate disassembly along with DSF release. In vitro experiments showed that cytotoxicity of DSF could be enhanced by the presence of Zn2+, and further amplified when encapsulated into SF/DSF@ZnO nanocomposites. It was confirmed that the significantly amplified cytotoxicity of SF/DSF@ZnO was resulted from pH-triggered Zn2+ release, inhibited cell migration, and increased ROS production. In vivo study showed that SF/DSF@ZnO nanocomposites significantly increased the tumor accumulation and prolonged the retention time. In vivo antitumor experiments in the xenograft model showed that SF/DSF@ZnO exerted the highest tumor-inhibition rate among all the drug treatments. Therefore, this exquisite study established silk fibroin-modified disulfiram/zinc oxide nanocomposites, SF/DSF@ZnO, where ZnO not only acted as a delivery carrier but also served as a metal ion reservoir to achieve synergistic antitumor efficacy. The established DSF nanoformulation displayed excellent therapeutic potential in future cancer treatment.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81903551, 81772316, 81803443]; Key Research and Development Program of Zhejiang Province [2018C03013]; Zhejiang Province Natural Science FoundationNatural Science Foundation of Zhejiang Province [LQ19H300001, LY19H180001, LY17H180008]; Zhejiang provincial program for the cultivation of high-level innovative health talents; 151 talent project of Zhejiang province; 551 talent projects of Wenzhou; Wenzhou Municipal Science and Technology Bureau [Y20190177, Y20180180, Y20180208]
出版者	AMER CHEMICAL SOC
出版地	WASHINGTON
ISSN	1543-8384
EISSN	1543-8392
卷号	17 期号:10 页码:3857-3869
DOI	10.1021/acs.molpharmaceut.0c00604
页数	13
WOS类目	Medicine, Research & Experimental ; Pharmacology & Pharmacy
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
WOS记录号	WOS:000580389300018
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	32833457
SCOPUSEID	2-s2.0-85092681358
通讯作者地址	[Kou, Longfa]Department of Pharmacy,Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,325027,China ; [Yao, Qing]Department of Ultrasonography,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,32500,China
Scopus学科分类	Molecular Medicine;Pharmaceutical Science;Drug Discovery
引用统计	被引频次：12[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/13277
专题	药学院（分析测试中心）附属第二医院附属第一医院_超声影像科药学院（分析测试中心）_药学系第二临床医学院、附属第二医院、育英儿童医院研究生工作部（研究生院）第二临床医学院、附属第二医院、育英儿童医院_影像医学与核医学_超声科其他_附属温岭医院（温岭市第一人民医院）
通讯作者	Kou, Longfa; Yao, Qing
作者单位	1.Department of Ultrasonography,First Affiliated Hospital of Wenzhou Medical University,Wenzhou, Zhejiang,32500,China; 2.School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 3.Department of Pharmacy,Affiliated Wenling Hospital of Wenzhou Medical University,Wenling,317500,China; 4.Department of Pharmacy,Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University,Wenzhou,325027,China; 5.Department of Ultrasonography,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang,32500,China
第一作者单位	附属第一医院; 药学院（分析测试中心）
通讯作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Zhao, Ying-Zheng,Lin, Meng-Ting,Lan, Qing-Hua,et al. Silk Fibroin-Modified Disulfiram/Zinc Oxide Nanocomposites for pH Triggered Release of Zn2+ and Synergistic Antitumor Efficacy[J]. MOLECULAR PHARMACEUTICS,2020,17(10):3857-3869.
APA	Zhao, Ying-Zheng., Lin, Meng-Ting., Lan, Qing-Hua., Zhai, Yuan-Yuan., Xu, He-Lin., ... & Yao, Qing. (2020). Silk Fibroin-Modified Disulfiram/Zinc Oxide Nanocomposites for pH Triggered Release of Zn2+ and Synergistic Antitumor Efficacy. MOLECULAR PHARMACEUTICS, 17(10), 3857-3869.
MLA	Zhao, Ying-Zheng,et al."Silk Fibroin-Modified Disulfiram/Zinc Oxide Nanocomposites for pH Triggered Release of Zn2+ and Synergistic Antitumor Efficacy".MOLECULAR PHARMACEUTICS 17.10(2020):3857-3869.