title: Targeted DNA delivery to cancer cells using a biotinylated chitosan carrier.
abstract: A novel biotinylated chitosan-graft-polyethyleneimine (Bio-Chi-g-PEI) copolymer was synthesized and evaluated as a nonviral gene delivery carrier for improvement of the transfection efficiency, endosomal escape, and targeted gene delivery of a plasmid encoding green fluorescent protein N1 (pEGFP-N1) into two different biotin-overexpressing cell lines including HeLa and OVCAR-3 cells. The structure of the obtained copolymers was confirmed by1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy. Physicochemical properties of the Bio-Chi-g-PEI/plasmid DNA (pDNA) complexes such as complex stability, size, zeta potential, and their morphology were investigated at various weight ratios of copolymer to pDNA. Bio-Chi-g-PEI copolymers could effectively condense pDNA into small particles with average diameters less than 164 nm and the zeta potential of +34.8 mV at the N/P ratio of 40/1. As revealed by flow cytometry, Bio-Chi-g-PEI/pDNA complexes had lower cytotoxicity than that of PEI 25 kDa/pDNA complexes in both cell lines. In vitro experiments revealed that the Bio-Chi-gPEI/pDNA complexes not only had much lower cytotoxicity, but also displayed higher transfection efficiency than that of PEI 25kDa/pDNA complexes. High percentage of cancer cells was successfully transfected by Bio-Chi-g-PEI/pDNA and properly expressed GFP protein. This study indicates that this copolymer complex can be a promising gene delivery carrier.
authors.affiliation: Nanobiotechnology Research Center, Baqiyatallah University of Medical Science, Tehran, Iran.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Darvishi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Nomani
authors.affiliation: Department of Nanobiotechnology, Faculty of Bioscience, Tarbiat Modares University, Tehran, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Hashemzadeh
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.affiliation: National Cell Bank of Iran (NCBI), Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Shokrgozar
authors.affiliation: Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, Iran.|Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D001710:Biotin / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry*; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010957:Plasmids / Q000737:chemistry / Q000494:pharmacology
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001710:Biotin; D048271:Chitosan
keywords: DNA delivery; chitosan linked PEI; copolymer synthesis; gene nanocarriers; nanoparticle; nonviral vectors