TY - JOUR
T1 - Polymeric Gene Carriers Bearing Pendant β-Cyclodextrin
T2 - The Relevance of Glycoside Permethylation on the "in Vitro" Cell Response
AU - Redondo, Juan Alfonso
AU - Martínez-Campos, Enrique
AU - Plet, Laetitia
AU - Pérez-Perrino, Mónica
AU - Navarro, Rodrigo
AU - Corrales, Guillermo
AU - Pandit, Abhay
AU - Reinecke, Helmut
AU - Gallardo, Alberto
AU - López-Lacomba, José Luis
AU - Fernández-Mayoralas, Alfonso
AU - Elvira, Carlos
N1 - Publisher Copyright:
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - cationic polymers
KW - cyclodextrins
KW - gene therapy
KW - nonviral gene vectors
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U2 - 10.1002/marc.201500647
DO - 10.1002/marc.201500647
M3 - Article
C2 - 26833583
AN - SCOPUS:84962434234
SN - 1022-1336
VL - 37
SP - 575
EP - 583
JO - Macromolecular Rapid Communications
JF - Macromolecular Rapid Communications
IS - 7
ER -