title: 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.
authors.affiliation: Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Li
authors.forename: Yubo
authors.initials: Y
authors.lastname: Guo
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Kuang
authors.forename: Sai
authors.initials: S
authors.lastname: An
authors.forename: Haojun
authors.initials: H
authors.lastname: Ma
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005910:Glioma / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000648:ultrastructure; D023041:Xenograft Model Antitumor Assays
chemical_list: D026901:Membrane Transport Proteins; C065637:choline transporter; D004317:Doxorubicin
keywords: Cancer therapy; Choline transporter; Co-delivery; Dual targeting; Nanoparticles