TY - JOUR
T1 - Hydroxyl versus permethylated glycopolymers as gene carriers
AU - Redondo, Juan Alfonso
AU - Martínez-Campos, Enrique
AU - Navarro, Rodrigo
AU - Pérez-Perrino, Mónica
AU - Reinecke, Helmut
AU - Gallardo, Alberto
AU - Corrales, Guillermo
AU - Fernández-Mayoralas, Alfonso
AU - Elvira, Carlos
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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.
KW - Gene therapy
KW - Glucose
KW - Polymers
KW - Transfection
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U2 - 10.1016/j.ejpb.2017.04.001
DO - 10.1016/j.ejpb.2017.04.001
M3 - Article
C2 - 28385616
AN - SCOPUS:85017281786
SN - 0939-6411
VL - 117
SP - 68
EP - 76
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -