Alkyl sulfonyl derivatized PAMAM-G2 dendrimers as nonviral gene delivery vectors with improved transfection efficiencies Morales Sanfrutos, Julia Megía Fernández, Alicia Hernández Mateo, Fernando Girón González, María Dolores Salto González, Rafael Santoyo González, Francisco PAMAM Dendrimers Gene transfection Financial Support was provided by Direccion General de Investigacion Cientıfica y Tecnica (DGICYT) (CTQ2008-01754) Junta de Andalucıa (P07-FQM-02899) and Fundacion Marcelino Botın. J. M.-S. thanks the University of Granada for a research contract (Programa Puente). A. M.-F. thanks the Spanish Ministerio de Educacion for a research fellowship (FPU). 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 LipofectAMINETM 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. 2024-01-24T13:02:02Z 2024-01-24T13:02:02Z 2011 journal article Org. Biomol. Chem., 2011, 9, 851–864 https://hdl.handle.net/10481/87216 10.1039/c0ob00355g eng embargoed access The Royal Society of Chemistry