Abstract |
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.
|
Authors | Jianfeng Li, Yubo Guo, Yuyang Kuang, Sai An, Haojun Ma, Chen Jiang |
Journal | Biomaterials
(Biomaterials)
Vol. 34
Issue 36
Pg. 9142-8
(Dec 2013)
ISSN: 1878-5905 [Electronic] Netherlands |
PMID | 23993342
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2013 Elsevier Ltd. All rights reserved. |
Chemical References |
- Membrane Transport Proteins
- choline transporter
- Doxorubicin
|
Topics |
- Animals
- Body Weight
(drug effects)
- Brain Neoplasms
(diagnosis, drug therapy)
- Cell Death
(drug effects)
- Cell Line, Tumor
- Diagnostic Imaging
- Doxorubicin
(pharmacology, therapeutic use)
- Drug Delivery Systems
- Endocytosis
(drug effects)
- Glioma
(diagnosis, drug therapy)
- Humans
- In Situ Nick-End Labeling
- Male
- Membrane Transport Proteins
(metabolism)
- Mice
- Mice, Nude
- Nanoparticles
(ultrastructure)
- Xenograft Model Antitumor Assays
|