title: FGF receptor-mediated gene delivery using ligands coupled to PEI-β-CyD.
abstract: A novel vector with high gene delivery efficiency and special cell-targeting ability was developed using a good strategy that utilized low-molecular-weight polyethylenimine (PEI; molecular weight: 600 KDa [PEI600]) crosslinked to β-cyclodextrin (β-CyD) via a facile synthetic route. Fibroblast growth factor receptors (FGFRs) are highly expressed in a variety of human cancer cells and are potential targets for cancer therapy. In this paper, CY11 peptides, which have been proven to combine especially with FGFRs on cell membranes were coupled to PEI-β-CyD using N-succinimidyl-3-(2-pyridyldithio) propionate as a linker. The ratios of PEI600, β-CyD, and peptide were calculated based on proton integral values obtained from the (1)H-NMR spectra of the resulting products. Electron microscope observations showed that CY11-PEI-β-CyD can efficiently condense plasmid DNA (pDNA) into nanoparticles of about 200 nm, and MTT assays suggested the decreased toxicity of the polymer. Experiments on gene delivery efficiency in vitro showed that CY11-PEI-β-CyD/pDNA polyplexes had significantly greater transgene activities than PEI-β-CyD/pDNA in the COS-7 and HepG2 cells, which positively expressed FGFR, whereas no such effect was observed in the PC-3 cells, which negatively expressed FGFR. Our current research indicated that the synthesized nonviral vector shows improved gene delivery efficiency and targeting specificity in FGFR-positive cells.
authors.affiliation: Center for Translational Medicine Research and Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shen Zhen, Guangdong 518055, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Hu
authors.forename: Guping
authors.initials: G
authors.lastname: Tang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Cheng
authors.forename: Ye
authors.initials: Y
authors.lastname: Yue
authors.forename: Jinchao
authors.initials: J
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001709:Biotechnology; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry* / Q000494:pharmacology; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D008024:Ligands; D010455:Peptides; D017468:Receptors, Fibroblast Growth Factor; D047392:beta-Cyclodextrins; D011094:Polyethyleneimine