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学科主题: 药学
题名:
The impact of a chlorotoxin-modified liposome system on receptor MMP-2 and the receptor-associated protein ClC-3
作者: 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
发表日期: 2014-07-01
DOI: 10.1016/j.biomaterials.2014.03.077
卷: 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
所属项目编号: 81130059 ; 2009CB930300 ; BMU20110263 ; 2013CB932501
项目资助者: 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)
WOS记录号: WOS:000336694700027
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54456
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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