High transfection efficiency promoted by tailor-made cationic tri-block copolymer-based nanoparticles.

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(β-amino ester) (PDMAEMA-b-PβAE-b-PDMAEMA), the influence of the PβAE 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-PβAE-b-PDMAEMA block copolymers for an extremely effective non-viral vector. The block copolymer PDMAEMA3000-b-PβAE12000-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).

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Cordeiro RA,Santo D,Farinha D,Serra A,Faneca H,Coelho JFJ

doi

10.1016/j.actbio.2016.10.015

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

113-123

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(16)30542-6

journal_volume

47

pub_type

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