title: Peptide-like Polymers Exerting Effective Glioma-Targeted siRNA Delivery and Release for Therapeutic Application.
abstract: Lipopolymer 49, a solid-phase synthesized T-shaped peptide-like oligoamide containing two central oleic acids, 20 aminoethane, and two terminal cysteine units, is identified as very potent and biocompatible small interfering RNA (siRNA) carrier for gene silencing in glioma cells. This carrier is combined with a novel targeting polymer 727, containing a precise sequence of Angiopep 2 targeting peptide, linked with 28 monomer units of ethylene glycol, 40 aminoethane, and two terminal cysteines in siRNA complex formation. Angiopep-polyethylene glycol (PEG)/siRNA polyplexes exhibit good nanoparticle features, effective glioma-targeting siRNA delivery, and intracellular siRNA release, resulting in an outstanding gene downregulation both in glioma cells and upon intravenous delivery in glioma model nude mice without significant biotoxicity. Therefore, this novel siRNA delivery system is expected to be a promising strategy for targeted and safe glioma therapy.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Sai
authors.initials: S
authors.lastname: An
authors.affiliation: Pharmaceutical Biotechnology, Center for Nanoscience, Ludwig-Maximilians-University Munich, Butenandtstrasse 5-13, 81377, Munich, Germany.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: He
authors.affiliation: Pharmaceutical Biotechnology, Center for Nanoscience, Ludwig-Maximilians-University Munich, Butenandtstrasse 5-13, 81377, Munich, Germany.
authors.forename: Ernst
authors.initials: E
authors.lastname: Wagner
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Jiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002232:Carbocyanines / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015536:Down-Regulation; D016503:Drug Delivery Systems; D004587:Electrophoresis, Agar Gel; D004705:Endocytosis / Q000187:drug effects; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011108:Polymers / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D010455:Peptides; D011108:Polymers; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols
keywords: BAG3; RNA delivery; glioma therapy; glutathione triggered; peptide-like polymer; siRNA; targeted therapy