title: Polymeric Gene Carriers Bearing Pendant β-Cyclodextrin: The Relevance of Glycoside Permethylation on the "In Vitro" Cell Response.
abstract: The incorporation of cyclodextrins (CDs) to nonviral cationic polymer vectors is very attractive due to recent studies that report a clear improvement of their cytocompatibility and transfection efficiency. However, a systematic study on the influence of the CD derivatization is still lacking. In this work, the relevance of β-CD permethylation has been addressed by preparing and evaluating two series of copolymers of the cationic N-ethyl pyrrolidine methacrylamide (EPA) and styrenic units bearing pendant hydroxylated and permethylated β-CDs (HCDSt and MeCDSt, respectively). For both cell lines, CDs permethylation shows a strong influence on plasmid DNA complexation, "in vitro" cytocompatibility and transfection efficiency of the resulting copolymers over two murine cell lines. While the incorporation of the hydroxylated CD moiety increased the cytotoxicity of the copolymers in comparison with their homopolycationic counterpart, the permethylated copolymers have shown full cytocompatibility as well as superior transfection efficiency than the controls. This behavior has been related to the different chemical nature of both units and tentatively to a different distribution of units along the polymeric chains. Cellular internalization analysis with fluorescent copo-lymers supports this behavior.
authors.affiliation: 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: Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.|Université Pierre et Marie Curie, 4, Place Jussieu, 75005, Paris, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Plet
authors.affiliation: 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: 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: 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: Network of Excellence for Functional Biomaterials, National University of Ireland, Newcastle Road, Galway, Ireland.
authors.forename: Abhay
authors.initials: A
authors.lastname: Pandit
authors.affiliation: 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: 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 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: José Luis
authors.initials: JL
authors.lastname: López-Lacomba
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: Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Elvira
mesh_terms: D016475:3T3 Cells; D000178:Acrylamides / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002412:Cations / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry; D008745:Methylation; D051379:Mice; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D014162:Transfection; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000178:Acrylamides; D001672:Biocompatible Materials; D002412:Cations; D006027:Glycosides; D011108:Polymers; D047392:beta-Cyclodextrins; C031215:betadex; C045985:methacrylamide
keywords: cationic polymers; cyclodextrins; gene therapy; nonviral gene vectors