title: Terminal modification on mPEG-dendritic poly-(l)-lysine cationic diblock copolymer for efficient gene delivery.
abstract: The development of new non-viral gene vectors with the advantages of low cytotoxicity and high gene transfection efficiency is a recent trend in gene therapy. In this work, we developed a series of termini-modified mPEG-dendritic poly-(l)-lysine cationic diblock copolymers (mPEG5k-DPL4-CG) by coupling various cationic groups to the dendritic skeleton. Their molecular structures were characterized by (1)H NMR, and the buffering capacities were measured by acid titration. The plasmid DNA (pDNA) binding affinities of the mPEG5k-DPL4-CG copolymers were investigated by EB displacement and agarose gel retardation assay, and the average particle size and surface charge of the polyplexes were analyzed by dynamic light scattering. Cytotoxicity and in vitro gene transfection were evaluated in several cell lines in the presence and absence of serum by the luciferase expression assay. The results indicated that the low molecular weight polyethylenimine (PEI800) termini-modified copolymer, mPEG5k-DPL4-PEI800, possessed high pDNA binding affinity, low cytotoxicity, and high gene transfection capability which were maintained in the presence of serum (10% FBS). It is worth noting that the gene delivery efficiency of the dendritic poly-(l)-lysine gene vector was enhanced by termini modification of suitable cationic blocks. The low cytotoxicity and serum-resistance properties of mPEG5k-DPL4-PEI800 make it a potential long-circulating gene vector in gene therapy applications.
authors.affiliation: a Laboratory for Polymer Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road, Shanghai , 200032 , China .
authors.forename: Ruilong
authors.initials: R
authors.lastname: Sheng
authors.forename: Kejia
authors.initials: K
authors.lastname: Xia
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
authors.forename: Amin
authors.initials: A
authors.lastname: Cao
mesh_terms: D000818:Animals; D002021:Buffers; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry / Q000235:genetics; D003712:Dendrites / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D002021:Buffers; D004337:Drug Carriers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011107:Polylysine; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D004247:DNA; D008156:Luciferases