title: Structurally flexible triethanolamine core PAMAM dendrimers are effective nanovectors for DNA transfection in vitro and in vivo to the mouse thymus.
abstract: With the aim of developing dendrimer nanovectors with a precisely controlled architecture and flexible structure for DNA transfection, we designed PAMAM dendrimers bearing a triethanolamine (TEA) core, with branching units pointing away from the center to create void spaces, reduce steric congestion, and increase water accessibility for the benefit of DNA delivery. These dendrimers are shown to form stable nanoparticles with DNA, promote cell uptake mainly via macropinocytosis, and act as effective nanovectors for DNA transfection in vitro on epithelial and fibroblast cells and, most importantly, in vivo in the mouse thymus, an exceedingly challenging organ for immune gene therapy. Collectively, these results validate our rational design approach of structurally flexible dendrimers with a chemically defined structure as effective nanovectors for gene delivery, and demonstrate the potential of these dendrimers in intrathymus gene delivery for future applications in immune gene therapy.
authors: Aix-Marseille Université, Centre Interdisciplinaire de Nanoscience de Marseille, CNRS UPR 3118, Département de Chimie, Marseille, France.
authors: Xiaoxuan
authors: X
authors: Liu
authors: Jiangyu
authors: J
authors: Wu
authors: Miriam
authors: M
authors: Yammine
authors: Jiehua
authors: J
authors: Zhou
authors: Paola
authors: P
authors: Posocco
authors: Stephane
authors: S
authors: Viel
authors: Cheng
authors: C
authors: Liu
authors: Fabio
authors: F
authors: Ziarelli
authors: Maurizio
authors: M
authors: Fermeglia
authors: Sabrina
authors: S
authors: Pricl
authors: Genevieve
authors: G
authors: Victorero
authors: Catherine
authors: C
authors: Nguyen
authors: Patrick
authors: P
authors: Erbacher
authors: Jean-Paul
authors: JP
authors: Behr
authors: Ling
authors: L
authors: Peng
mesh_terms: D000818:Animals; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D050091:Dendrimers / Q000737:chemistry*; D004983:Ethanolamines / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000378:metabolism*; D014162:Transfection
chemical_list: D050091:Dendrimers; D004983:Ethanolamines; C104700:PAMAM Starburst; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004247:DNA; C009546:triethanolamine