title: Hydroxyl versus permethylated glycopolymers as gene carriers.
abstract: The main parameters that contribute to non-viral gene delivery are chemical structure and charge distribution. Indeed, saccharide units have been reported to have specific interactions with proteins located in the outer leaflet of the plasma cell membrane that facilitate the cellular internalization of plasmid-DNA vector complexes. In this work, glycopolymers based on statistical copolymers were synthesized through radical copolymerization of a cationic unit, N-ethyl pyrrolidine methacrylamide (EPA), with two styrenic monomers derived from the hydroxylated and permethylated forms of α-glucose. These copolymers were evaluated as possible non-viral gene carriers, and their ability to complex DNA was evaluated. The transfection efficiency and cytocompatibility of the polyplexes, in both fibroblastic and tumoral murine cell lines, was evaluated. Systems derived from α-glucose (GLCSt), over a monomer concentration range of 5-70mol%, exhibited high toxicity and low transfection efficiency, and were not able to significantly improve on results obtained from positive poly-EPA (PEPA) and polyethyleneimine (PEI) controls. However, systems derived from the permethylated form of α-glucose (MGLCSt), formed stable complexes with DNA or polyplexes, which showed improved transfection efficiency and cytocompatibility in comparison to positive controls. The high transfection efficiency can be clearly attributed to their cytocompatibility, which was notably found to be different for Swiss fibroblasts and B16 melanoma cells, high for Swiss and low for B16. As such, we present permethylated MCLCSt copolymers as good candidates for the possible development of therapies against melanoma.
authors.affiliation: Department of Applied Macromolecular Chemistry, Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Juan Alfonso
authors.initials: JA
authors.lastname: Redondo
authors.affiliation: Institute of Biofunctional Studies (IEB), Tissue Engineering Group, (UCM), Associated Unit to the Institute of Polymer Science and Technology (CSIC), Paseo de Juan XXIII 1, 28040 Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Martínez-Campos
authors.affiliation: Department of Applied Macromolecular Chemistry, Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Navarro
authors.affiliation: Department of Applied Macromolecular Chemistry, Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Pérez-Perrino
authors.affiliation: Department of Applied Macromolecular Chemistry, Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Helmut
authors.initials: H
authors.lastname: Reinecke
authors.affiliation: Department of Applied Macromolecular Chemistry, Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Gallardo
authors.affiliation: Institute of Organic Chemistry, IQOG-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Corrales
authors.affiliation: Institute of Organic Chemistry, IQOG-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Mayoralas
authors.affiliation: Department of Applied Macromolecular Chemistry, Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain. Electronic address: celvira@ictp.csic.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Elvira
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006579:Heterozygote; D008546:Melanoma, Experimental; D051379:Mice; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011108:Polymers
keywords: Gene therapy; Glucose; Polymers; Transfection