High transfection efficiency promoted by tailor-made cationic tri-block copolymer-based nanoparticles.
Acta Biomater
; 47: 113-123, 2017 01 01.
Article
em En
| MEDLINE
| ID: mdl-27744070
ABSTRACT
Cationic polymer-based vectors have been considered a promising strategy in gene therapy area due to their inherent ability to condense genetic material and successfully transfect cells. However, they usually exhibit high cytotoxicity. In this work, it is proposed the use of a tailor-made gene carrier based on a tri-block copolymer of poly[2-(dimethylamino)ethyl methacrylate] and poly(ß-amino ester) (PDMAEMA-b-PßAE-b-PDMAEMA), the influence of the PßAE length being assessed. For this purpose, three different block copolymers were prepared varying the molecular weight of this segment. The obtained materials were characterized by NMR and SEC analyzes. Different polyplexes formulations were prepared and evaluated in terms of physicochemical characterization (ethidium bromide intercalation assay, agarose gel electrophoresis assay, dynamic light scattering, zeta potential analyzes and atomic force microscopy) and biological activity (cytotoxicity, and luciferase and green fluorescent protein expression in Hela and COS-7 cell lines). Among the developed nanosystems, the best polyplex formulation revealed between 40- and 60-fold higher transgene expression, in HeLa and COS-7 cell lines, and much lower cytotoxicity than that observed with branched PEI and TurboFect™. Moreover, these nanosystems present suitable physicochemical properties for gene delivery namely reduced mean diameter and high DNA protection. The results reported here show the enormous potential of this block copolymer as gene carrier. STATEMENT OF SIGNIFICANCE:
Syntheses of PDMAEMA-b-PßAE-b-PDMAEMA block copolymers for an extremely effective non-viral vector. The block copolymer PDMAEMA3000-b-PßAE12000-b-PDMAEMA3000-based polyplexes at 100/1N/P ratio exhibits between 40- and 60-fold higher transgene expression in HeLa and COS-7 cell lines than commonly used polymeric non-viral vectors, namely branched PEI (known as the gold standard) and TurboFect™ (commercial available).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polímeros
/
Transfecção
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Nanopartículas
Limite:
Animals
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Humans
Idioma:
En
Revista:
Acta Biomater
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Portugal