PMID- 26677726 OWN - NLM STAT- MEDLINE DCOM- 20161024 LR - 20181202 IS - 1520-5827 (Electronic) IS - 0743-7463 (Linking) VI - 32 IP - 2 DP - 2016 Jan 19 TI - Efficient Condensation of DNA into Environmentally Responsive Polyplexes Produced from Block Catiomers Carrying Amine or Diamine Groups. PG - 577-86 LID - 10.1021/acs.langmuir.5b04080 [doi] AB - The 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-PDPA50), poly(ethylene oxide)113-b-poly[2-(diethylamino)ethyl methacrylate]50 (PEO113-b-PDEA50), poly[oligo(ethylene glycol)methyl ether methacrylate]70-b-poly[oligo(ethylene glycol)methyl ether methacrylate10-co-2-(diethylamino)ethyl methacrylate47-co-2-(diisopropylamino)ethyl methacrylate47] (POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47), and poly[oligo(ethylene glycol)methyl ether methacrylate]70-b-polyoligo(ethylene glycol)methyl ether methacrylate10-co-2-methylacrylic acid 2-[(2-(dimethylamino)ethyl)methylamino]ethyl ester44 (POEGMA70-b-P(OEGMA10-co-DAMA44). Block copolymers PEO113-b-PDEA50 and POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47) were evidenced to properly condense DNA into particles with a desirable size for cellular uptake via endocytic pathways (R(H) approximately 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 POEGMA70-b-P(OEGMA10-co-DEA47-co-DPA47) condenses DNA more efficiently and with higher thermodynamic outputs than does PEO113-b-PDEA50. 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. FAU - Albuquerque, Lindomar J C AU - Albuquerque LJ AD - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , Santo Andre 09210-170, Brazil. FAU - Annes, Kelly AU - Annes K AD - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , Santo Andre 09210-170, Brazil. FAU - Milazzotto, Marcella P AU - Milazzotto MP AD - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , Santo Andre 09210-170, Brazil. FAU - Mattei, Bruno AU - Mattei B AD - Departamento de Biofisica, Universidade Federal de Sao Paulo , Sao Paulo 04021-001, Brazil. FAU - Riske, Karin A AU - Riske KA AD - Departamento de Biofisica, Universidade Federal de Sao Paulo , Sao Paulo 04021-001, Brazil. FAU - Jager, Eliezer AU - Jager E AD - Institute of Macromolecular Chemistry AS CR , 162 06 Prague, Czech Republic. FAU - Panek, Jiri AU - Panek J AD - Institute of Macromolecular Chemistry AS CR , 162 06 Prague, Czech Republic. FAU - Stepanek, Petr AU - Stepanek P AD - Institute of Macromolecular Chemistry AS CR , 162 06 Prague, Czech Republic. FAU - Kapusta, Peter AU - Kapusta P AD - J. Heyrovsky Institute of Physical Chemistry, 182 23 Prague, Czech Republic. FAU - Muraro, Paulo I R AU - Muraro PI AD - Departamento de Quimica, Universidade Federal de Santa Maria , Santa Maria 97105-900, Brazil. FAU - De Freitas, Augusto G O AU - De Freitas AG AD - Departamento de Quimica, Universidade Federal de Santa Maria , Santa Maria 97105-900, Brazil. FAU - Schmidt, Vanessa AU - Schmidt V AD - Departamento de Quimica, Universidade Federal de Santa Maria , Santa Maria 97105-900, Brazil. FAU - Giacomelli, Cristiano AU - Giacomelli C AD - Departamento de Quimica, Universidade Federal de Santa Maria , Santa Maria 97105-900, Brazil. FAU - Bonvent, Jean-Jacques AU - Bonvent JJ AD - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , Santo Andre 09210-170, Brazil. FAU - Giacomelli, Fernando C AU - Giacomelli FC AD - Centro de Ciencias Naturais e Humanas, Universidade Federal do ABC , Santo Andre 09210-170, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160104 PL - United States TA - Langmuir JT - Langmuir : the ACS journal of surfaces and colloids JID - 9882736 RN - 0 (Methacrylates) RN - 0 (Polymethacrylic Acids) RN - 0 (poly(2-(diisopropylamino)ethyl methacrylate)) RN - 0 (polyethylene glycol methacrylate) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 9007-49-2 (DNA) SB - IM MH - Calorimetry MH - DNA/*chemistry MH - Endocytosis MH - *Gene Transfer Techniques MH - Humans MH - Methacrylates/*chemistry MH - Microscopy, Atomic Force MH - Nucleic Acid Conformation MH - Polyethylene Glycols/*chemistry MH - Polymethacrylic Acids/*chemistry MH - Thermodynamics EDAT- 2015/12/19 06:00 MHDA- 2016/10/25 06:00 CRDT- 2015/12/19 06:00 PHST- 2015/12/19 06:00 [entrez] PHST- 2015/12/19 06:00 [pubmed] PHST- 2016/10/25 06:00 [medline] AID - 10.1021/acs.langmuir.5b04080 [doi] PST - ppublish SO - Langmuir. 2016 Jan 19;32(2):577-86. doi: 10.1021/acs.langmuir.5b04080. Epub 2016 Jan 4.