Preparation of well-defined brush-like block copolymers for gene delivery applications under biorelevant reaction conditions

[Display omitted] •Synthesis of well-defined bock copolymers under biorelevant reaction conditions.•Evaluation of block copolymers as non-viral gene vectors of plasmid DNA (pDNA).•Complexation of polymers with pDNA, high encapsulation efficiencies, no cytotoxicity.•Delivery of pDNA into nucleus of c...

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Veröffentlicht in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2018-09, Vol.169, p.107-117
Hauptverfasser: Góis, Joana R., Reis, Fábio, Almeida, Ana M., Pereira, Patrícia, Sousa, Fani, Serra, Arménio C., Coelho, Jorge F.J.
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Sprache:eng
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Zusammenfassung:[Display omitted] •Synthesis of well-defined bock copolymers under biorelevant reaction conditions.•Evaluation of block copolymers as non-viral gene vectors of plasmid DNA (pDNA).•Complexation of polymers with pDNA, high encapsulation efficiencies, no cytotoxicity.•Delivery of pDNA into nucleus of cervical cancer cells (in vitro experiments). Well-defined oligo(ethylene glycol) methyl ether methacrylate (OEOMA) based block copolymers with cationic segments composed by N,N-(dimethylamino) ethyl methacrylate (DMAEMA) and/or 2-(diisopropylamino) ethyl methacrylate (DPA) were developed under biorelevant reaction conditions. These brush-type copolymers were synthesized through supplemental activator and reducing agent (SARA) atom transfer radical polymerization (ATRP) using sodium dithionite as SARA agent. The synthesis was carried out using an eco-friendly solvent mixture, very low copper catalyst concentration, and mild reaction conditions. The structure of the block copolymers was characterized by size exclusion chromatography (SEC) analysis and 1H nuclear magnetic resonance (NMR) spectroscopy. The pH-dependent protonation of these copolymers enables the efficient complexation with plasmid DNA (pDNA), yielding polyplexes with sizes ranging from 200 up to 700 nm, depending on the molecular weight of the copolymers, composition and concentration used. Agarose gel electrophoresis confirmed the successful pDNA encapsulation. No cytotoxicity effect was observed, even for N/P ratios higher than 50, for human fibroblasts and cervical cancer cell lines cells. The in vitro cellular uptake experiments demonstrated that the pDNA-loaded block copolymers were efficiently delivered into nucleus of cervical cancer cells. The polymerization approach, the unique structure of the block copolymers and the efficient DNA encapsulation presented can open new avenues for development of efficient tailor made gene delivery systems under biorelevant conditions.
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2018.05.004