Modified polyamidoamine based nanoparticles for tumor cell gene delivery

<p>Polyamidoamine is a cationic dendrimer with the ability to condense plasmid DNA into nanometric particles suitable for gene transfer applications. Toxicity is one of the obstacles in wide range usage of this dendrimer in cancer gene therapy. The toxicity is mainly associated with high density of positive charge on its surface which leads to cell membrane disruption. Therefore, modification of the dendrimer backbone to reduce the positive charge might be useful in order to decrease the dendrimer cytotoxicity. To achieve this goal, a series of hydrophobic derivatives of PAMAM was prepared by reacting with ethyl, butyl, hexyl and lauryl acrylates. By these modifications the surface positive charge was modulated and the hydrophobic balance of the dendrimer was improved. DNA binding affinity test and gel retardation assay demonstrated that the modified dendrimers bind to plasmid DNA efficiently. Particle size and zeta potential measurements showed that these modified polymers are able to form nanoparticles smaller than 200 nm with reduced zeta potential compared with the unmodified PAMAM. Evaluation of cytotoxicity was carried out in HepG2, MCF7 and NIH3T3 cell lines by MTT method. The results showed that the cytotoxicity of modified dendrimers and the dendrimer/plasmid complexes (dendriplexes) reduced significantly. Therefore, it is expected that the modified dendrimers will have much potential as a good candidate for gene delivery.<br> <br>