Efficient Condensation of DNA into Environmentally Responsive Polyplexes Produced from Block Catiomers Carrying Amine or Diamine Groups

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dc.citation.issue2
dc.citation.volume32
dc.contributor.authorAlbuquerque, Lindomar J. C.
dc.contributor.authorAnnes, Kelly
dc.contributor.authorMilazzotto, Marcella P.
dc.contributor.authorMattei, Bruno [UNIFESP]
dc.contributor.authorRiske, Karin A. [UNIFESP]
dc.contributor.authorJaeger, Eliezer
dc.contributor.authorPanek, Jiri
dc.contributor.authorStepanek, Petr
dc.contributor.authorKapusta, Peter
dc.contributor.authorMuraro, Paulo I. R.
dc.contributor.authorDe Freitas, Augusto G. O.
dc.contributor.authorSchmidt, Vanessa
dc.contributor.authorGiacomelli, Cristiano
dc.contributor.authorBonvent, Jean-Jacques
dc.contributor.authorGiacomelli, Fernando C.
dc.coverageWashington
dc.date.accessioned2020-10-30T18:46:38Z
dc.date.available2020-10-30T18:46:38Z
dc.date.issued2016
dc.description.abstractThe intracellular delivery of nucleic acids requires a vector system as they cannot diffuse across lipid membranes. Although polymeric transfecting agents have been extensively investigated, none of the proposed gene delivery vehicles fulfill all of the requirements needed for an effective therapy, namely, the ability to bind and compact DNA into polyplexes, stability in the serum environment, endosome-disrupting capacity, efficient intracellular DNA release, and low toxicity. The challenges are mainly attributed to conflicting properties such as stability vs efficient DNA release and toxicity vs efficient endosome-disrupting capacity. Accordingly, investigations aimed at safe and efficient therapies are still essential to achieving gene therapy clinical success. Taking into account the mentioned issues, herein we have evaluated the DNA condensation ability of poly(ethylene oxide)(113)-b-poly[2-(diisopropylamino)ethyl methacrylate](50) (PEO113-b-PDPA(50)), poly(ethylene oxide)(113)-b-poly[2-(diethylamino)ethyl methacrylate](50) (PEO113-b-PDEA(50)), poly[oligo(ethylene glycol)methyl ether methacrylate](70)-b-poly[oligo(ethylene glycol)methyl ether methacrylate(10-)co-2-(diethylamino)ethyl methacrylate(47)-co-2-(diisopropylamino)ethyl methacrylate(47)] (POEGMA(70)-b-P(OEGMA(10)-co-DEA(47)-co-DPA(47)), and poly[oligo(ethylene glycol)methyl ether methacrylate](70)-b-poly{oligo(ethylene glycol)methyl ether methacrylate(10)-co-2-methylacrylic acid 2-[(2-(dimethylamino)ethyl)methylamino]ethyl ester(44)} (POEGMA(70)-b-P(OEGMA(10)-co-DAMA(44)). Block copolymers PEO113-b-PDEA(50) and POEGMA(70)-b-P(OEGMA(10)-co-DEA(47)-co-DPA(47)) were evidenced to properly condense DNA into particles with a desirable size for cellular uptake via endocytic pathways (R-H similar to 65-85 nm). The structure of the polyplexes was characterized in detail by scattering techniques and atomic force microscopy. The isothermal titration calorimetric data revealed that the polymer/DNA binding is endothermic; therefore, the process in entropically driven. The combination of results supports that POEGMA(70)-b-P(OEGMA(10)-co-DEA(47)-co-DPA(47)) condenses DNA more efficiently and with higher thermodynamic outputs than does PEO113-b-PDEA(50). Finally, circular dichroism spectroscopy indicated that the conformation of DNA remained the same after complexation and that the polyplexes are very stable in the serum environment.en
dc.description.affiliationUniv Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 Santo Andre, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, BR-04021001 Sao Paulo, Brazil
dc.description.affiliationAS CR, Inst Macromol Chem, Prague 16206, Czech Republic
dc.description.affiliationJ Heyrovsky Inst Phys Chem, Prague 18223, Czech Republic
dc.description.affiliationUniv Fed Santa Maria, Dept Quim, BR-97105900 Santa Maria, RS, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biofis, BR-04021001 Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPESP
dc.description.sponsorshipCNPq
dc.description.sponsorshipMinistry of Education, Youth and Sports of the Czech Republic
dc.description.sponsorshipIDFAPESP: 2014/22983-9
dc.description.sponsorshipIDCNPq: 470608/2012-9
dc.description.sponsorshipIDMinistry of Education, Youth and Sports of the Czech Republic: LH14292
dc.format.extent577-586
dc.identifierhttps://doi.org/10.1021/acs.langmuir.5b04080
dc.identifier.citationLangmuir. Washington, v. 32, n. 2, p. 577-586, 2016.
dc.identifier.doi10.1021/acs.langmuir.5b04080
dc.identifier.issn0743-7463
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/58548
dc.identifier.wosWOS:000368563700023
dc.language.isoeng
dc.publisherAmer Chemical Soc
dc.relation.ispartofLangmuir
dc.rightsAcesso restrito
dc.titleEfficient Condensation of DNA into Environmentally Responsive Polyplexes Produced from Block Catiomers Carrying Amine or Diamine Groupsen
dc.typeArtigo
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