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The impact of a chlorotoxin-modified liposome system on receptor MMP-2 and the receptor-associated protein ClC-3
Qin, Chao1,2; He, Bing1; Dai, Wenbing1; Lin, Zhiqiang1; Zhang, Hua1; Wang, Xueqing1; Wang, Jiancheng1; Zhang, Xuan1; Wang, Guangji2; Yin, Lifang1,2; Zhang, Qiang1
关键词Chlorotoxin Targeting Drug Delivery System Mmp-2 Cic-3 Receptor-associated Protein
刊名BIOMATERIALS
2014-07-01
DOI10.1016/j.biomaterials.2014.03.077
35期:22页:5908-5920
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Engineering, Biomedical ; Materials Science, Biomaterials
研究领域[WOS]Engineering ; Materials Science
关键词[WOS]INTERSTITIAL FLUID PRESSURE ; MEMBRANE-PROTEINS ; CHLORIDE CHANNELS ; DRUG-DELIVERY ; GENE DELIVERY ; TUMOR MICROENVIRONMENT ; MASS-SPECTROMETRY ; CELL INVASION ; SOLID TUMORS ; HUMAN GLIOMA
英文摘要

Currently, it is unknown whether a receptor-associated protein will be affected when a ligand modified delivery system interacts with its receptor. Besides, chlorotoxin (ClTx)-modified liposomes can target to glioma cells, but the target molecule is not clear: MMP-2, ClC-3 or both? Here a comparative study of ClTx-conjugated liposomes was conducted on two types of tumor cells: U87, a human glioma cell line with high expression of both MMP-2 and ClC-3, and A549, a human lung cancer cell line with expression of only MMP-2. ClTx-modified liposomes behaved similarly in these two cancer cells in terms of in vitro cell uptake, endocytosis pathway, intracellular trafficking and in vivo targeting efficacy, though the two tested cell lines were very different in ClC-3 expression. These results revealed that the targeted delivery of ClTx modified liposomes to U87 tumor was MMP-2-mediated and not correlated with the chloride channel ClC-3. On the other hand, ClTx modified on the liposomes did activate the receptor-associated protein ClC-3 via the binding with MMP-2, leading to the inhibition on cell migration and chloride currents. This is significant because cell migration is a key step in tumor metastasis. Interestingly, higher in vitro cellular uptake and lower in vivo tumor accumulation of liposomal systems was found in U87 compared to the A549 model, possibly due to the biological differences between in vitro and in vivo models. In general, ClTx-modified delivery systems may potentially target to tumors other than glioma that express a high level of MMP-2, and its effect on ClC-3 may help prevent tumor metastasis. (C) 2014 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000336694700027
项目编号81130059 ; 2009CB930300 ; BMU20110263 ; 2013CB932501
资助机构National Natural Science Foundation of China ; National Research Fund for Fundamental Key Project ; Innovation Team of Ministry of Education ; National Basic Research Program of China (973 program)
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54456
专题北京大学药学院
北京大学基础医学院
北京大学药学院_药剂学系
作者单位1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.China Pharmaceut Univ, Sch Pharm, Key Lab Drug Metab & Pharmacokinet, Nanjing 210009, Jiangsu, Peoples R China
推荐引用方式
GB/T 7714
Qin, Chao,He, Bing,Dai, Wenbing,et al. The impact of a chlorotoxin-modified liposome system on receptor MMP-2 and the receptor-associated protein ClC-3[J]. BIOMATERIALS,2014,35(22):5908-5920.
APA Qin, Chao.,He, Bing.,Dai, Wenbing.,Lin, Zhiqiang.,Zhang, Hua.,...&Zhang, Qiang.(2014).The impact of a chlorotoxin-modified liposome system on receptor MMP-2 and the receptor-associated protein ClC-3.BIOMATERIALS,35(22),5908-5920.
MLA Qin, Chao,et al."The impact of a chlorotoxin-modified liposome system on receptor MMP-2 and the receptor-associated protein ClC-3".BIOMATERIALS 35.22(2014):5908-5920.
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