Issue 3, 2011

Alkyl sulfonyl derivatized PAMAM-G2dendrimers as nonviral gene delivery vectors with improved transfection efficiencies

Abstract

Amphiphilic dendrimer-based gene delivery vectors bearing peripheral alkyl sulfonyl hydrophobic tails were constructed using low-generation PAMAM-G2 as the core and functionalized by means of the aza-Michael type addition of its primary amino groups to vinylsulfone derivatives as an efficient tool for surface engineering. While the unmodified PAMAM-G2 was unable to efficiently transfect eukaryotic cells, functionalized PAMAM-G2 dendrimers were able to bind DNA at low N/P ratios, protect DNA from digestion with DNase I and showed high transfection efficiencies and low cytotoxicity. Dendrimers with a C18 alkyl chain produced transfection efficiencies up to 3.1 fold higher than LipofectAMINE™ 2000 in CHO-k1 cells. The dendriplexes based in functionalized PAMAM-G2 also showed the ability to retain their transfection properties in the presence of serum and the ability to transfect different eukaryotic cell lines such as Neuro-2A and RAW 264.7. Taking advantage of the vinylsulfone chemistry, fluorescent PAMAM-G2 derivatives of these vectors were prepared as molecular probes to determine cellular uptake and internalization through a clathrin-independent mechanism.

Graphical abstract: Alkyl sulfonyl derivatized PAMAM-G2 dendrimers as nonviral gene delivery vectors with improved transfection efficiencies

Supplementary files

Article information

Article type
Paper
Submitted
30 Jun 2010
Accepted
14 Oct 2010
First published
30 Nov 2010

Org. Biomol. Chem., 2011,9, 851-864

Alkyl sulfonyl derivatized PAMAM-G2 dendrimers as nonviral gene delivery vectors with improved transfection efficiencies

J. Morales-Sanfrutos, A. Megia-Fernandez, F. Hernandez-Mateo, M. xmlns="http://www.rsc.org/schema/rscart38"> <. D. Giron-Gonzalez, R. Salto-Gonzalez and F. Santoyo-Gonzalez, Org. Biomol. Chem., 2011, 9, 851 DOI: 10.1039/C0OB00355G

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