title: Poly(amidoamine) Dendrimers Modified with 1,2-Epoxyhexane or 1,2-Epoxydodecane for Enhanced Gene Delivery Applications.
abstract: We report a new non-viral gene delivery system based on hydrophobically modified poly(amidoamine) (PAMAM) dendrimers. In this study, the periphery of amine-terminated generation 5 (G5) PAMAM dendrimers was partially reacted with 1,2-epoxyhexane and 1,2-epoxydodecane, respectively. The formed hydrophobically modified G5 dendrimers (denoted as G5.NH2-C6 or G5.NH2-C12) were used to complex two different plasmid DNAs (pDNAs) encoding luciferase (Luc) and enhanced green fluorescent protein (EGFP), respectively for gene transfection studies. The polyplexes formed between vectors and pDNA were characterized by gel retardation assay, dynamic light scattering, and zeta potential measurements. We show that the G5.NH2-C6 and G5.NH2-C12 vectors are able to effectively compact the pDNA, allowing for highly efficient gene transfection into a model cell line (HeLa cells) as demonstrated by both Luc assay and confocal microscopic imaging of the EGFP expression. Under the studied N/P ratios (the molar ratio of primary amines of the dendrimers to phosphates in the pDNA backbone) at 2.5 or 5, the transfection efficiency of the dendrimer-based vectors followed the order of G5.NH2-C12 > G5.NH2-C6 > G5.NH2. This enhanced gene transfection capacity is believed to be associated with the enhanced hydrophobic interaction between the vector/pDNA complexes and the relatively hydrophobic cell membranes. The developed hydrophobically modified dendrimers may be used as a promising non-viral vector for enhanced gene delivery applications.
authors.forename: Tongyu
authors.initials: T
authors.lastname: Xiao
authors.forename: Xueyan
authors.initials: X
authors.lastname: Cao
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Hou
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.forename: Jieru
authors.initials: J
authors.lastname: Qiu
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
mesh_terms: D002470:Cell Survival; D050091:Dendrimers / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D011073:Polyamines / Q000737:chemistry*; D014162:Transfection
chemical_list: D050091:Dendrimers; D004852:Epoxy Compounds; C531249:Poly(amidoamine); D011073:Polyamines; C419870:1,2-epoxyhexane