Combination of Poly[(2-dimethylamino)ethyl methacrylate] and Poly(β-amino ester) Results in a Strong and Synergistic Transfection Activity

This work reports an innovative and very effective gene delivery nanosystem, based on the combination of poly[(2-dimethylamino)ethyl methacrylate] (PDMAEMA) and poly(β-amino ester) (PβAE) homopolymers, that has the capacity to efficiently deliver genetic material into target cells, even in the presence of serum. The best formulation, prepared with the combination PDMAEMA/4PβAE at the 25/1 nitrogen/phosphate (N/P) ratio, presented a 700-fold and 220-fold higher transfection activity than that obtained with branched polyethylenimine (PEI)-based polyplexes and block copolymer-based polyplexes, respectively. This new nanocarrier revealed high transgene expression in different human cells, including hard-to-transfect normal human astrocytes. The polyplexes presented high protection of genetic material and reduced sizes, which are suitable physicochemical properties for in vivo applications. Overall, this study demonstrates that the combination of PDMAEMA and PβAE homopolymers resulted in a noticeable and synergistic effect in terms of transfection activity, without causing substantial toxicity, constituting a new platform for the development of gene delivery nanosystems.