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