title: Biocompatible anionic polyelectrolyte for improved liposome based gene transfection.
abstract: Cationic liposomes have been widely used as efficient gene carriers. However, the serious cytotoxicity caused by exposed positive charges restricts the further application of those kinds of gene vectors. Thus, it is challenging to develop biocompatiable non-positive charge carriers to achieve high gene transfection efficiencies. Herein, we report a novel design by pasting biocompatible anionic polyelectrolyte, namely alginic acid, hyaluronic acid, pectin and polyglutamic acid, to the positive charge surface of liposome/pDNA complex. Through shielding the positive charges, the new gene carriers show decreased cytotoxicity while still maintaining high transfection efficiency. To be noted, the complex formed by coating polyglutamic acid to the surface of liposome/pDNA greatly enhanced the transfection efficiency in HepG2 cells, and the use of pectin shows increased transfection in MCF-7 cells. Hemolysis assay proved a possible mechanism that when the new gene complex was internalized into cells, as acidity increases, more side chains become hydrophobic, and thus destabilizing the endosomal membrane to accelerate DNA escape. The present results suggest that such anionic polyelectrolyte covered liposome based carrier possess promising application for clinical gene delivery.
authors.affiliation: Innovative Drug Research Centre, Chongqing University, Chongqing 401331, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Innovative Drug Research Centre, Chongqing University, Chongqing 401331, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Innovative Drug Research Centre, Chongqing University, Chongqing 401331, China.
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Qu
authors.affiliation: Innovative Drug Research Centre, Chongqing University, Chongqing 401331, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Innovative Drug Research Centre, Chongqing University, Chongqing 401331, China.
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Long
authors.affiliation: Innovative Drug Research Centre, Chongqing University, Chongqing 401331, China. Electronic address: fengxuli@cqu.edu.cn.
authors.forename: Xuli
authors.initials: X
authors.lastname: Feng
mesh_terms: D000464:Alginates / Q000737:chemistry; D000838:Anions / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry; D004573:Electrolytes / Q000737:chemistry*; D018014:Gene Transfer Techniques; D020723:Glucuronic Acid / Q000737:chemistry; D006367:HeLa Cells; D056945:Hep G2 Cells; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D010368:Pectins / Q000737:chemistry; D010957:Plasmids / Q000737:chemistry; D011099:Polyglutamic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014162:Transfection / Q000379:methods
chemical_list: D000464:Alginates; D000838:Anions; D001672:Biocompatible Materials; D002412:Cations; D004573:Electrolytes; D006603:Hexuronic Acids; D008081:Liposomes; D011108:Polymers; D011099:Polyglutamic Acid; D010368:Pectins; D020723:Glucuronic Acid; D006820:Hyaluronic Acid; D004247:DNA
keywords: Anionic polyelectrolyte; Biocompatibility; Endosomal escape; Gene transfection; Liposome