1. Choline transporter-targeting and co-delivery system for glioma therapy.
- Author
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Li, Jianfeng, Guo, Yubo, Kuang, Yuyang, An, Sai, Ma, Haojun, and Jiang, Chen
- Subjects
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CHOLINE , *GLIOMA treatment , *DRUG delivery systems , *CANCER treatment , *GENE therapy , *CANCER chemotherapy , *TUMOR necrosis factors , *BLOOD-brain barrier - Abstract
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. [Copyright &y& Elsevier]
- Published
- 2013
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