Polymeric gene carriers bearing pendant β-cyclodextrin: the relevance of glycoside permethylation on the 'in vitro' cell response

Autor: Alberto Gallardo, Rodrigo Navarro, Mónica Pérez-Perrino, Alfonso Fernández-Mayoralas, Abhay Pandit, José Luis López-Lacomba, Laetitia Plet, Enrique Martínez-Campos, Carlos Elvira, Guillermo Corrales, Juan Alfonso Redondo, Helmut Reinecke
Přispěvatelé: European Commission, Consejo Superior de Investigaciones Científicas (España)
Rok vydání: 2016
Předmět:
nonviral gene vectors
Polymers and Plastics
Cationic polymers
Polymers
pyrrolidine
Library science
Biocompatible Materials
click clusters
02 engineering and technology
European Social Fund
010402 general chemistry
delivery vectors
Methylation
01 natural sciences
Mice
Gene therapy
Cations
Political science
Materials Chemistry
Gamma-cyclodextrin
Animals
European commission
Glycosides
alpha-cyclodextrin
Acrylamides
Cyclodextrins
therapy
cyclodextrins
Gene carrier
beta-Cyclodextrins
Organic Chemistry
cholesterol
3T3 Cells
021001 nanoscience & nanotechnology
polyamidoamine dendrimer
gene therapy
0104 chemical sciences
Microscopy
Fluorescence

transfection
Research council
Spectrophotometry
Ultraviolet

Cell response
0210 nano-technology
gamma-cyclodextrins
Nonviral gene vectors
cationic polymers
Plasmids
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
BASE-Bielefeld Academic Search Engine
Popis: 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 copolymers supports this behavior.
The authors gratefully acknowledge support from Grants MAT-2010-20001, MAT2013-42957-R, CSD2009-00088 (Consolider project), SAF2011-27863, 201280E091 (CSIC intramural project) and PI10/02985FIS (Seventh Framework Programme of the European Commission, EuroNanomed ERA-NET initiative, REBONE project). J.A.R. and R.N. gratefully acknowledges funding from the Spanish Research Council (CSIC) and European Social Fund (ESF) through the JAE program
Databáze: OpenAIRE