title: A Simple Zn2+ Complex-Based Composite System for Efficient Gene Delivery.
abstract: Metal complexes might become a new type of promising gene delivery systems because of their low cytotoxicity, structural diversity, controllable aqua- and lipo-solubility, and appropriate density and distribution of positive charges. In this study, Zn2+ complexes (1-10) formed with a series of ligands contained benzimidazole(bzim)were prepared and characterized. They were observed to have different affinities for DNA, dependent on their numbers of positive charges, bzim groups, and coordination structures around Zn2+. The binding induced DNA to condensate into spherical nanoparticles with ~ 50 nm in diameter. The cell transfection efficiency of the DNA nanoparticles was poor, although they were low toxic. The sequential addition of the cell-penetrating peptide (CPP) TAT(48-60) and polyethylene glycol (PEG) resulted in the large DNA condensates (~ 100 nm in diameter) and the increased cellular uptake. The clathrin-mediated endocytosis was found to be a key cellular uptake pathway of the nanoparticles formed with or without TAT(48-60) or/and PEG. The DNA nanoparticles with TAT(48-60) and PEG was found to have the cell transfection efficiency up to 20% of the commercial carrier Lipofect. These results indicated that a simple Zn2+-bzim complex-based composite system can be developed for efficient and low toxic gene delivery through the combination with PEG and CPPs such as TAT.
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education and School of Chemistry, Central China Normal University, Wuhan, 430079, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education and School of Chemistry, Central China Normal University, Wuhan, 430079, China.
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education and School of Chemistry, Central China Normal University, Wuhan, 430079, China.
authors.forename: Xianggao
authors.initials: X
authors.lastname: Meng
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education and School of Chemistry, Central China Normal University, Wuhan, 430079, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education and School of Chemistry, Central China Normal University, Wuhan, 430079, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education and School of Chemistry, Central China Normal University, Wuhan, 430079, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pesticide and Chemical Biology, Ministry of Education and School of Chemistry, Central China Normal University, Wuhan, 430079, China.
authors.forename: Changlin
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000378:metabolism; D019556:COS Cells; D002413:Cations, Divalent; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism; D002522:Chlorocebus aethiops; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004705:Endocytosis; D018014:Gene Transfer Techniques; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D014162:Transfection; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D002413:Cations, Divalent; D057846:Cell-Penetrating Peptides; D056831:Coordination Complexes; D008055:Lipids; C086724:Lipofectamine; D010446:Peptide Fragments; D054322:tat Gene Products, Human Immunodeficiency Virus; D011092:Polyethylene Glycols; D004247:DNA; D015032:Zinc