2024-03-28T11:10:20Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1498642023-01-20T13:09:30Zcom_10261_33com_10261_5com_10261_56com_10261_3col_10261_286col_10261_309
DIGITAL.CSIC
author
Redondo, Juan A.
author
Martínez-Campos, Enrique
author
Navarro, Rodrigo
author
Pérez-Perrino, Mónica
author
Reinecke, Helmut
author
Gallardo Ruiz, Alberto
author
Corrales, Guillermo
author
Fernández-Mayoralas, Alfonso
author
Elvira, Carlos
funder
Ministerio de Economía y Competitividad (España)
funder
Consejo Superior de Investigaciones Científicas (España)
funder
European Commission
2017-05-17T10:56:06Z
2017-05-17T10:56:06Z
2017
European Journal of Pharmaceutics and Biopharmaceutics 117: 68-76 (2017)
http://hdl.handle.net/10261/149864
10.1016/j.ejpb.2017.04.001
http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/501100003339http://dx.doi.org/10.13039/501100000780
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 5–70 mol%, 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.
eng
closedAccess
Polymers
Gene therapy
Transfection
Glucose
Hydroxyl versus permethylated glycopolymers as gene carriers
artículo
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URL
https://digital.csic.es/bitstream/10261/149864/1/accesoRestringido.pdf
File
MD5
42637ae8545636bc41605c1740a9a84e
15753
application/pdf
accesoRestringido.pdf