title: The strategy to improve gene transfection efficiency and biocompatibility of hyperbranched PAMAM with the cooperation of PEGylated hyperbranched PAMAM.
abstract: As a promising non-viral gene vector, cationic polyamidoamine (PAMAM) dendrimer could form complexes with negative charged DNA to mediate efficient gene delivery in vitro and in vivo. However, complicated synthesis technology and potential cytotoxicity limited their application in clinical translational researches. Hyperbranched polyamidoamine (h-PAMAM), which could be synthesized by a simpler one-pot method, has similar properties with PAMAM, and PEGylation modification of h-PAMAM has been used to reduce cytotoxicity. Here we prepared gene delivery system with h-PAMAM and h-PAMAM derivative h-PAMAM-g-PEG, respectively and found that the viability of cells with h-PAMAM-g-PEG was quite higher in comparison with cells with unmodified h-PAMAM. However, gene delivery efficiency was lower with h-PAMAM-g-PEG. Then we used mixture composed of h-PAMAM and h-PAMAM-g-PEG and such composition was designed to reduce cytotoxicity while maintaining high transfection efficiency. Our results indicated that this mixture system of h-PAMAM and h-PAMAM-g-PEG achieved higher transfection efficiency and lower cytotoxicity compared with h-PAMAM-only system.
authors: State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Yangfei
authors: Y
authors: Sun
authors: State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors: Yunfeng
authors: Y
authors: Jiao
authors: State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
authors: Yang
authors: Y
authors: Wang
authors: State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai 200433, China.
authors: Daru
authors: D
authors: Lu
authors: State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Fudan University, Shanghai 200433, China. Electronic address: wlyang@fudan.edu.cn.
authors: Wuli
authors: W
authors: Yang
mesh_terms: D021581:Active Transport, Cell Nucleus; D001672:Biocompatible Materials; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D050091:Dendrimers / Q000138:chemical synthesis / Q000378:metabolism* / Q000633:toxicity; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000378:metabolism* / Q000633:toxicity; D014162:Transfection / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D050091:Dendrimers; C104700:PAMAM Starburst; C522249:PEG-PAMAM; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D004247:DNA
keywords: Cytotoxicity; Gene delivery; Hyperbranched polyamidoamine; Mixture system; PEGylation