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学科主题: 药学
题名:
Mechanisms of co-modified liver-targeting liposomes as gene delivery carriers based on cellular uptake and antigens inhibition effect
作者: Zhang, Yuan1; Qi, Xian Rong1; Gao, Yan1; Wei, Lai1; Maitani, Yoshie1; Nagai, Tsuneji1
关键词: beta-sitosterol-beta-D-glucoside ; liver-targeting ; co-modified cationic liposomes ; membrane fusion ; endocytosis
刊名: JOURNAL OF CONTROLLED RELEASE
发表日期: 2007-02-12
DOI: 10.1016/j.jconrel.2006.11.006
卷: 117, 期:2, 页:281-290
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: SOYBEAN-DERIVED STERYLGLUCOSIDE ; CATIONIC LIPOSOMES ; IN-VIVO ; ANTISENSE OLIGONUCLEOTIDES ; DRUG-DELIVERY ; HEPATITIS ; SYSTEM ; OLIGODEOXYNUCLEOTIDES ; BIODISTRIBUTION ; REPLICATION
英文摘要:

In order to deliver antisense oligonucleotides (asODN) into hepatocytes orientedly in the treatment of hepatitis B virus (HBV) infection, the liver-targeting cationic liposomes was developed as a gene carrier, which was co-modified with the ligand of the asialoglycoprotein receptor (ASGPR), beta-sitosterol-beta-D-glucoside (sito-G) and the nonionic surfactant, Brij 35. Flow cytometry (FCM) analysis and enzyme-linked immunosorbent assay (ELISA) showed that the asODN-encapsulating cationic liposomes exhibited high transfection efficiency and strong antigens inhibition effect in primary rat hepatocytes and HepG2.2.15 cells, respectively. With the help of several inhibitors acting on different steps during the targeting lipofection, the cellular uptake mechanisms of the co-modified liver-targeting cationic liposomes were investigated through antigens inhibition effect assay and confocal laser scanning microscopy (CLSM) analysis. The cellular uptake with high transfection efficiency seemed to involve both endocytosis and membrane fusion. The ligand sito-G was confirmed to be able to enhance ASGPR-mediated endocytosis, the nonionic surfactant Brij 35 seemed to be able to facilitate membrane fusion, and the co-modification resulted in the most efficient transfection but no enhanced cytotoxicity. These results suggested that the co-modified liver-targeting cationic liposomes would be a specific and effective carrier to transfer asODN into hepatocytes infected with HBV orientedly. (c) 2006 Elsevier B.V. All rights reserved.

语种: 英语
WOS记录号: WOS:000244624100017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/49921
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, Beijing 100083, Peoples R China
2.Peking Univ, Peoples Hosp, Inst Hepatol, Beijing 100044, Peoples R China
3.Hoshi Univ, Inst Med Chem, Shinagawa Ku, Tokyo 1428501, Japan

Recommended Citation:
Zhang, Yuan,Qi, Xian Rong,Gao, Yan,et al. Mechanisms of co-modified liver-targeting liposomes as gene delivery carriers based on cellular uptake and antigens inhibition effect[J]. JOURNAL OF CONTROLLED RELEASE,2007,117(2):281-290.
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