title: Synergistic effect of amino acids modified on dendrimer surface in gene delivery.
abstract: Design of an efficient gene vector based on dendrimer remains a great challenge due to the presence of multiple barriers in gene delivery. Single-functionalization on dendrimer cannot overcome all the barriers. In this study, we synthesized a list of single-, dual- and triple-functionalized dendrimers with arginine, phenylalanine and histidine for gene delivery using a one-pot approach. The three amino acids play different roles in gene delivery: arginine is essential in formation of stable complexes, phenylalanine improves cellular uptake efficacy, and histidine increases pH-buffering capacity and minimizes cytotoxicity of the cationic dendrimer. A combination of these amino acids on dendrimer generates a synergistic effect in gene delivery. The dual- and triple-functionalized dendrimers show minimal cytotoxicity on the transfected NIH 3T3 cells. Using this combination strategy, we can obtain triple-functionalized dendrimers with comparable transfection efficacy to several commercial transfection reagents. Such a combination strategy should be applicable to the design of efficient and biocompatible gene vectors for gene delivery.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.
authors.forename: Yitong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.
authors.forename: Naimin
authors.initials: N
authors.lastname: Shao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China. Electronic address: yycheng@mail.ustc.edu.cn.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004247:DNA / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D010957:Plasmids; D014162:Transfection
chemical_list: D000596:Amino Acids; D050091:Dendrimers; D004247:DNA
keywords: Amino acid; Dendrimer; Gene delivery; Synergistic effect