Angiopep-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma

被引:324
|
作者
Xin, Hongliang
Jiang, Xinyi
Gu, Jijin
Sha, Xianyi
Chen, Liangcen
Law, Kitki
Chen, Yanzuo
Wang, Xiao
Jiang, Ye
Fang, Xiaoling [1 ]
机构
[1] Fudan Univ, Key Lab Smart Drug Delivery, Minist Educ, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
Dual targeting; Angiopep; LRP; Blood-brain barrier; Brain glioma; PTX; DENSITY-LIPOPROTEIN RECEPTOR; POLY(EPSILON-CAPROLACTONE) NANOPARTICLES; BIODEGRADABLE POLYMERSOMES; VECTOR ANGIOPEP-2; PHASE-II; IN-VITRO; BARRIER; PACLITAXEL; PROTEIN; CELLS;
D O I
10.1016/j.biomaterials.2011.02.044
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Dual-targeting nanoparticle drug delivery system was developed by conjugating Angiopep with PEG-PCL nanoparticles (ANG-NP) through bifunctional PEG to overcome the limitations of low transport of chemotherapeutics across the Blood-brain barrier (BBB) and poor penetration into tumor tissue. ANG-NP can target the low-density lipoprotein receptor-related protein (LRP) which is over-expressed on the BBB and glioma cells. Compared with non-targeting nanoparticles, a significantly higher amount of rhodamine isothiocyanate-labeled dual-targeting nanoparticles were endocytosed by 1.187 MG cells. The antiproliferative and cell apoptosis assay of paclitaxel-loaded ANG-NP (ANG-NP-PTX) demonstrated that ANG-NP-PTX resulted in enhanced inhibitory effects to U87 MG glioma cells. The transport ratios across the BBB model in vitro were significantly increased and the cell viability of U87 MG glioma cells after crossing the BBB was obviously decreased by ANG-NP-PTX Enhanced accumulation of ANG-NP in the glioma bed and infiltrating margin of intracranial U87 MG glioma tumor-bearing in vivo model were observed by real time fluorescence image. In conclusion, Angiopep-conjugated PEG-PCL nanoparticles were prospective in dual-targeting drug delivery system for targeting therapy of brain glioma. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4293 / 4305
页数:13
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