TY - JOUR
T1 - Complexation and release of DNA in polyplexes formed with reducible linear poly(β-amino esters)
AU - Rata-Aguilar, Azahara
AU - Segovia-Ramos, Nathaly
AU - Jódar-Reyes, Ana Belén
AU - Ramos-Pérez, Víctor
AU - Borrós, Salvador
AU - Martín-Rodríguez, Antonio
AU - Ortega-Vinuesa, Juan Luis
N1 - Funding Information:
The authors wish to express their appreciation for the financial support granted by the following research projects: MAT2013-43922-R–European FEDER support included–(MICINN, Spain), and P10-CTS-6270 (Junta de Andalucía, Spain), CEIBiotic 20F12/16. Azahara Rata-Aguilar thanks the Government of Spain (MECD) for her FPU fellowship.
Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Designing nanocarriers for gene delivery is a multidisciplinary challenge that involves not only DNA condensation with biocompatible polymers, but also DNA-release processes. Once the genetic material is introduced into the cell, the rupture of degradable bonds permits the unpacking and release of the load. In this work, a dual-degradable polycation - composed by a linear poly(β-amino ester) chain in which ester and disulfide bonds coexist - has been used to condense a DNA plasmid. The goal was to reinforce the spontaneous hydrolysis of the ester groups with the intracellular break-up of the disulfide bonds, since these reducible bonds are degraded in the reductive intracellular environment. For a comparative study, two poly(β-amino ester) molecules differing only in the presence (or absence) of some S. S bonds have been tested. DNA condensation, physico-chemical characterization of the polyplexes formed, and degradation studies have been carried out at pH 5 and pH 7. The acidic conditions gave the best nanoparticles, due to a better solubilization of both polymers and to a higher stability of the ester bonds. Despite the synthesis and storage of polyplexes were much more appropriate at pH 5, transfection efficiency in HeLa cells was similar irrespective the original pH used. Only in those polyplexes formed at low polymer:DNA ratios (i.e. 5 and 10 (w/w)) was transfection more effective when the plasmid was condensed at an acidic pH. With regard to the DNA-release efficiency in the intracellular medium, degradation of the polymers was practically governed by the rapid hydrolysis of the ester groups, this spontaneous and rapid process masking, unfortunately, any potential contribution associated with the breakup of the disulfide bonds.
AB - Designing nanocarriers for gene delivery is a multidisciplinary challenge that involves not only DNA condensation with biocompatible polymers, but also DNA-release processes. Once the genetic material is introduced into the cell, the rupture of degradable bonds permits the unpacking and release of the load. In this work, a dual-degradable polycation - composed by a linear poly(β-amino ester) chain in which ester and disulfide bonds coexist - has been used to condense a DNA plasmid. The goal was to reinforce the spontaneous hydrolysis of the ester groups with the intracellular break-up of the disulfide bonds, since these reducible bonds are degraded in the reductive intracellular environment. For a comparative study, two poly(β-amino ester) molecules differing only in the presence (or absence) of some S. S bonds have been tested. DNA condensation, physico-chemical characterization of the polyplexes formed, and degradation studies have been carried out at pH 5 and pH 7. The acidic conditions gave the best nanoparticles, due to a better solubilization of both polymers and to a higher stability of the ester bonds. Despite the synthesis and storage of polyplexes were much more appropriate at pH 5, transfection efficiency in HeLa cells was similar irrespective the original pH used. Only in those polyplexes formed at low polymer:DNA ratios (i.e. 5 and 10 (w/w)) was transfection more effective when the plasmid was condensed at an acidic pH. With regard to the DNA-release efficiency in the intracellular medium, degradation of the polymers was practically governed by the rapid hydrolysis of the ester groups, this spontaneous and rapid process masking, unfortunately, any potential contribution associated with the breakup of the disulfide bonds.
KW - Biodegradable polymer
KW - Gene transfection
KW - Nonviral DNA carriers
KW - Polyplexes
KW - Reducible poly(β-amino ester)
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UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pure_univeritat_ramon_llull&SrcAuth=WosAPI&KeyUT=WOS:000359172600041&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1016/j.colsurfb.2015.06.001
DO - 10.1016/j.colsurfb.2015.06.001
M3 - Article
C2 - 26125487
AN - SCOPUS:84933060038
SN - 0927-7765
VL - 133
SP - 339
EP - 346
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
ER -