Choline transporter-targeting and co-delivery system for glioma therapy

被引：110

作者：

Li, Jianfeng ^{[1
]}

Guo, Yubo ^{[1
]}

Kuang, Yuyang ^{[1
]}

An, Sai ^{[1
]}

Ma, Haojun ^{[1
]}

Jiang, Chen ^{[1
]}

机构：

[1] Fudan Univ, Key Lab Smart Drug Delivery, Minist Educ, Dept Pharmaceut,Sch Pharm, Shanghai 201203, Peoples R China

来源：

BIOMATERIALS | 2013年 / 34卷 / 36期

基金：

中国国家自然科学基金;

关键词：

Cancer therapy; Choline transporter; Co-delivery; Dual targeting; Nanoparticles; PACLITAXEL; GENE; NANOPARTICLES; NANOPROBE; HTRAIL; TUMORS;

D O I：

10.1016/j.biomaterials.2013.08.030

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Combination of gene therapy and chemotherapy is a promising approach for glioma therapy. In this study, a co-delivery system of plasmid encoding human tumor necrosis factor-related apoptosis-inducing ligand (pORF-hTRAIL, Trail) and doxorubicin (DOX) has been simply constructed in two steps. Firstly, DOX was intercalated into Trail to form a stable complex. Secondly, DOX-Trail complex was condensed by Dendrigraft poly-L-lysine (DGL) to form a nanoscaled co-delivery system. Choline transporters are both expressed on blood brain barrier (BBB) and glioma, Herein, a choline derivate with high choline transporter affinity was chosen as BBB and glioma dual targeting ligand. Choline-derivate modified co-delivery system showed higher cellular uptake efficiency and cytotoxicity than unmodified co-delivery system in U87 MG cells. In comparison with single medication or unmodified delivery system, Choline-derivate modified co-delivery system induced more apoptosis both in vitro and in vivo. The therapeutic efficacy on U87 MG bearing xenografts further confirmed the predominance of this dual targeting and co-delivery system. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：9142 / 9148

页数：7

共 19 条

[1] Conjugation of doxorubicin to cell penetrating peptides sensitizes human breast MDA-MB 231 cancer cells to endogenous TRAIL-induced apoptosis [J].