title: MC8 peptide-mediated Her-2 receptor targeting based on PEI-β-CyD as gene delivery vector.
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]) cross-linked to β-cyclodextrin (β-CyD) via a facile synthetic route. Human epidermal growth factor receptor 2 (Her-2) are highly expressed in a variety of human cancer cells and are potential targets for cancer therapy. MC8 peptides, which have been proven to combine especially with Her-2 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 MC8-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 MC8-PEI-β-CyD/pDNA polyplexes had significantly greater transgene activities than PEI-β-CyD/pDNA in the Skov3 and A549 cells, which positively expressed Her-2, whereas, no such effect was observed in the MCF-7 cells, which negatively expressed Her-2. Our current research indicated that the synthesized nonviral vector shows improved gene delivery efficiency and targeting specificity in Her-2 positive cells.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Hefang
authors.initials: H
authors.lastname: Xiao
authors.forename: Xiangfu
authors.initials: X
authors.lastname: Zeng
authors.forename: Yiping
authors.initials: Y
authors.lastname: Hu
mesh_terms: D029681:Arabidopsis Proteins / Q000008:administration & dosage*; D003546:Cysteine Endopeptidases / Q000008:administration & dosage*; D004337:Drug Carriers / Q000138:chemical synthesis; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D061986:MCF-7 Cells; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D029681:Arabidopsis Proteins; D003546:Cysteine Endopeptidases; D004337:Drug Carriers; D011094:Polyethyleneimine; D018719:Erb-b2 Receptor Tyrosine Kinases; D047392:beta-Cyclodextrins; C527345:metacaspase-8, Arabidopsis