title: Surface-engineered dendrimers with a diaminododecane core achieve efficient gene transfection and low cytotoxicity.
abstract: Cationic dendrimers are widely used as gene vectors; however, these materials are usually associated with unsatisfied transfection efficiency and biocompatibility. In this study, we used an aliphatic hydrocarbon-cored polyamidoamine (PAMAM) dendrimer as an alternative to traditional cationic PAMAM dendrimers in the design of efficient gene vectors. Diaminododecane-cored generation 4 (C12G4) PAMAM dendrimer showed dramatically higher efficacy in luciferase and EGFP gene transfection than diaminoethane-cored generation 4 (C2G4) and diaminohexane-cored generation 4 (C6G4) PAMAM dendrimers. The viability of cells incubated with C12G4 at transfection concentrations is above 90%. The significantly improved gene transfection efficacy of C12G4 is attributed to the hydrophobic core of C12G4 which increases the cellular uptake of dendrimer/DNA polyplexes. Further modification of C12G4 with functional ligands such as arginine, 2,4-diamino-1,3,5-triazine, and fluorine compounds significantly increase its transfection efficiency on several cell lines. These results suggest that diaminododecane-cored dendrimers can be developed as a versatile scaffold in the design of efficient gene vectors.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University , Shanghai, 200241, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Naimin
authors.initials: N
authors.lastname: Shao
authors.forename: Mingming
authors.initials: M
authors.lastname: Wang
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wang
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000473:Alkanes / Q000737:chemistry* / Q000633:toxicity; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D013499:Surface Properties; D014162:Transfection
chemical_list: D000473:Alkanes; D050091:Dendrimers; C007548:n-dodecane