The transfection activity of non-viral vectors is highly dependent on the delivery capacity of the carriers. Therefore, the aim of this work was to evaluate the activity of a new PAMAM dendrimer-Transferrin conjugate (P-Tf) with improved gene delivery activity to cancer cells. The formulations containing the novel P-Tf were able to bind pDNA and protect it from the activity of DNAse I enzyme. Moreover, it formed nanoparticles with positive surface charge, although the presence of Tf led to a decrease of the zeta potential to almost electroneutral values. This new vector, formulated at N/P 6, exhibited excellent transfection efficacy in HeLa, HepG2 and CT26 cell lines, whereas in Neuro2A no improvement was achieved. Compared to control complexes with branched polyethylenimine (bPEI), targeted dendriplexes (complexes formed by cationic polymeric dendrimers and DNA) were more efficient in HepG2 and HeLa cells. Cellular viability was always kept over 80% in these cell lines with higher values than bPEI control polyplexes. The uptake via receptor-mediated endocytosis was ensured by a competition assay, by adding an excess of free Tf, which led to a decrease in the transfection activity of targeted dendriplexes.
Keywords: Gene therapy; Gene transfer; Nanoparticle; Nanotechnology; Polyamidoamine (PAMAM) dendrimers; Transferrin.
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