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

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.
AuthorsJianfeng Li, Yubo Guo, Yuyang Kuang, Sai An, Haojun Ma, Chen Jiang
JournalBiomaterials (Biomaterials) Vol. 34 Issue 36 Pg. 9142-8 (Dec 2013) ISSN: 1878-5905 [Electronic] Netherlands
PMID23993342 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 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

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