title: Enhanced bioactivity of internally functionalized cationic dendrimers with PEG cores.
abstract: Hybrid dendritic-linear block copolymers based on a 4-arm poly(ethylene glycol) (PEG) core were synthesized using an accelerated AB2/CD2 dendritic growth approach through orthogonal amine/epoxy and thiol-yne chemistries. The biological activity of these 4-arm and the corresponding 2-arm hybrid dendrimers revealed an enhanced, dendritic effect with an exponential increase in cell internalization concomitant with increasing amine end groups and low cytotoxicity. Furthermore, the ability of these hybrid dendrimers to induce endosomal escape combined with their facile and efficient synthesis makes them attractive platforms for gene transfection. The 4-arm-based dendrimer showed significantly improved DNA binding and gene transfection capabilities in comparison with the 2-arm derivative. These results combined with the MD simulation indicate a significant effect of both the topology of the PEG core and the multivalency of these hybrid macromolecules on their DNA binding and delivery capablities.
authors.affiliation: Materials Research Laboratory, University of California, Santa Barbara, California 93106-5121, United States.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Albertazzi
authors.forename: Frauke M
authors.initials: FM
authors.lastname: Mickler
authors.forename: Giovanni M
authors.initials: GM
authors.lastname: Pavan
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salomone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bardi
authors.forename: Mariangela
authors.initials: M
authors.lastname: Panniello
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Amir
authors.forename: Taegon
authors.initials: T
authors.lastname: Kang
authors.forename: Kato L
authors.initials: KL
authors.lastname: Killops
authors.forename: Christoph
authors.initials: C
authors.lastname: Bräuchle
authors.forename: Roey J
authors.initials: RJ
authors.lastname: Amir
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Hawker
mesh_terms: D002412:Cations / Q000737:chemistry*; D002470:Cell Survival; D004247:DNA / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics; D004996:Ethidium / Q000032:analysis; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D056004:Molecular Dynamics Simulation; D011092:Polyethylene Glycols / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection
chemical_list: D002412:Cations; D050091:Dendrimers; D011092:Polyethylene Glycols; D004247:DNA; D004996:Ethidium