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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.

Original publication

DOI

10.1021/bm301384y

Type

Journal article

Journal

Biomacromolecules

Publication Date

10/12/2012

Volume

13

Pages

4089 - 4097

Keywords

Cations, Cell Survival, DNA, Dendrimers, Ethidium, Gene Transfer Techniques, HeLa Cells, Humans, Magnetic Resonance Spectroscopy, Microscopy, Confocal, Molecular Dynamics Simulation, Polyethylene Glycols, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Transfection