title: A novel dendrimer based on poly (L-glutamic acid) derivatives as an efficient and biocompatible gene delivery vector.
abstract: Non-viral gene delivery systems based on cationic polymers have faced limitations related to their relative low gene transfer efficiency, cytotoxicity and system instability in vivo. In this paper, a flexible and pompon-like dendrimer composed of poly (amidoamine) (PAMAM) G4.0 as the inner core and poly (L-glutamic acid) grafted low-molecular-weight polyethylenimine (PLGE) as the surrounding multiple arms was synthesized (MGI dendrimer). The novel MGI dendrimer was designed to combine the merits of size-controlled PAMAM G4.0 and the low toxicity and flexible chains of PLGE. In phosphate-buffered saline dispersions the well-defined DNA/MGI complex above a N/P ratio of 30 showed good stability with particle sizes of approximately 200 nm and a comparatively low polydispersity index. However, the particle size of the DNA/25 kDa polyethylenimine (DNA/PEI 25K) complex was larger than 700 nm under the same salt conditions. The shielding of the compact amino groups at the periphery of flexible PAMAM and biocompatible PLGE chains in MGI resulted in a dramatic decrease of the cytotoxicity compared to native PAMAM G4.0 dendrimer. The in vitro transfection efficiency of DNA/MGI dendrimer complex was higher than that of PAMAM G4.0 dendrimer. Importantly, in serum-containing medium, DNA/MGI complexes at their optimal N/P ratio maintained the same high levels of transfection efficiency as in serum-free medium, while the transfection efficiency of native PAMAM G4.0, PEI 25K and Lipofectamine 2000 were sharply decreased. In vivo gene delivery of pVEGF165/MGI complex into balloon-injured rabbit carotid arteries resulted in significant inhibition of restenosis by increasing VEGF165 expression in local vessels. Therefore, the pompon-like MGI dendrimer may be a promising vector candidate for efficient gene delivery in vivo.
authors.affiliation: School of Pharmaceutical Sciences and the First Affiliated Hospital, Sun Yat-sen University, 80 Zhongshan Road II, Guangzhou 510080, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zeng
authors.forename: Shirong
authors.initials: S
authors.lastname: Pan
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Chi
authors.initials: C
authors.lastname: Wang
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wen
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wu
authors.forename: Cuifeng
authors.initials: C
authors.lastname: Wang
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Feng
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D016466:CHO Cells; D002470:Cell Survival; D002942:Circular Dichroism; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D003851:Deoxyribonucleases / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D058426:Neointima / Q000473:pathology; D010316:Particle Size; D010957:Plasmids / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry; D011099:Polyglutamic Acid / Q000737:chemistry*; D011817:Rabbits; D013055:Spectrophotometry, Infrared; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011099:Polyglutamic Acid; D011094:Polyethyleneimine; D004247:DNA; D003851:Deoxyribonucleases