title: Hyaluronic acid conjugated β-cyclodextrin-oligoethylenimine star polymer for CD44-targeted gene delivery.
abstract: A new CD44-targeted gene delivery system, the star-shaped cationic polymer containing a β-cyclodextrin (β-CD) core and multiple branched oligoethylenimine (OEI) arms with conjugated oligomer of hyaluronic acid (HA), was synthesized by reductive amination between β-CD-OEI star polymer and HA, and was characterized for pDNA condensation and nanoparticle formation, followed by evaluation for targeted gene delivery of luciferase reporter gene and wild type p53 gene in CD44-positive and CD44-negative cell lines. The β-CD-OEI-HA polymer contained 6 arms of OEI (600 Da) and a short HA segment. It could fully condense pDNA to form nanoparticles with sizes ranging from 100 to 200 nm at N/P ratios of 8 or higher. The conjugation of HA reduced cytotoxicity of β-CD-OEI-HA/pDNA polyplexes. It was found that CD44 receptor was highly expressed and localized at the membrane of MDA-MB-231 breast cancer cell line, while no CD44 was found at the membrane of MCF-7 epithelial cell line. Compared with PEI (25 kDa) and β-CD-OEI star polymers, β-CD-OEI-HA demonstrated significant increased gene transfection efficiency in MDA-MB-231 cells, while such effect was absent in MCF-7 cells. The targeted delivery of wild type p53 gene by β-CD-OEI-HA in MDA-MB-231 cells resulted in an increased cell cycle arrest at sub-G1 phase.
authors: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
authors: Hui
authors: H
authors: Yin
authors: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore.
authors: Feng
authors: F
authors: Zhao
authors: School of Medical Sciences, The University of Sydney, NSW 2006, Australia.
authors: Daohai
authors: D
authors: Zhang
authors: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 7 Engineering Drive 1, Singapore 117574, Singapore; Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research), 3 Research Link, Singapore 117602, Singapore. Electronic address: jun-li@nus.edu.sg.
authors: Jun
authors: J
authors: Li
mesh_terms: D001388:Aziridines / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics*; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001388:Aziridines; D018960:Hyaluronan Receptors; D011108:Polymers; D016159:Tumor Suppressor Protein p53; D047392:beta-Cyclodextrins; C033132:aziridine; D006820:Hyaluronic Acid; C031215:betadex
keywords: CD44 receptor; Cyclodextrin; Hyaluronic acid; Oligoethylenimine; Targeted gene delivery