title: DNA Transfection to Mesenchymal Stem Cells Using a Novel Type of Pseudodendrimer Based on 2,2-Bis(hydroxymethyl)propionic Acid.
abstract: In the search for effective vehicles to carry genetic material into cells, we present here new pseudodendrimers that consist of a hyperbranched polyester core surrounded by amino-terminated 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) dendrons. The pseudodendrimers are readily synthesized from commercial hyperbranched bis-MPA polyesters of the second, third, and fourth generations and third-generation bis-MPA dendrons, bearing eight peripheral glycine moieties, coupled by the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). This approach provides globular macromolecular structures bearing 128, 256, and 512 terminal amino groups, and these can complex pDNA. The toxicity of the three pseudodendrimers was studied on two cell lines, mesenchymal stem cells, and HeLa, and it was demonstrated that these compounds do not affect negatively cell viability up to 72 h. The complexation with DNA was investigated in terms of N-to-P ratio and dendriplex stability. The three generations were found to promote internalizing of pDNA into mesenchymal stem cells (MSCs), and their transfection capacity was compared with two nonviral commercial transfection agents, Lipofectamine and TransIT-X2. The highest generations were able to transfect these cells at levels comparable to both commercial reagents.
authors.affiliation: Departamento de Quı́mica Orgánica, Facultad de Ciencias, Instituto de Nanociencia de Aragón, Universidad de Zaragoza , Zaragoza 50009, Spain.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lancelot
authors.affiliation: Centro de Investigación Biomédica de Aragón, IIS Aragón , Zaragoza 50009, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: González-Pastor
authors.affiliation: Departamento de Quı́mica Orgánica, Facultad de Ciencias, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC , Zaragoza 50009, Spain.
authors.forename: Alberto
authors.identifier: 0000-0002-8932-9085
authors.initials: A
authors.lastname: Concellón
authors.affiliation: Departamento de Quı́mica Orgánica, Facultad de Ciencias, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC , Zaragoza 50009, Spain.
authors.forename: Teresa
authors.identifier: 0000-0001-7091-077X
authors.initials: T
authors.lastname: Sierra
authors.affiliation: Centro de Investigación Biomédica de Aragón, IIS Aragón, Fundación Araid, Universidad Francisco de Vitoria , Madrid 28223, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Martín-Duque
authors.affiliation: Departamento de Quı́mica Orgánica, Facultad de Ciencias, Instituto de Nanociencia de Aragón, Universidad de Zaragoza , Zaragoza 50009, Spain.
authors.forename: José L
authors.identifier: 0000-0001-9866-6633
authors.initials: JL
authors.lastname: Serrano
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010957:Plasmids; D011422:Propionates / Q000494:pharmacology*; D014162:Transfection / Q000379:methods*
chemical_list: D050091:Dendrimers; D006880:Hydroxy Acids; D011422:Propionates; C110034:2,2-bis(hydroxymethyl)-propionic acid