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TITLE:Gene Delivery and Immunomodulatory Effects of Plasmid DNA Associated with Branched Amphiphilic Peptide Capsules

Authors:L.A. Avila, L.R.M.M. Aps, N. Ploscariu, P. Sukthankar, R. Guo, K.E. Wilkinson, P. Games, R. Szoszkiewicz, R.P.S. Alves, M.O. Diniz, Y. Fang, L.C.S. Ferreira, J.M. Tomich

We recently reported on a new class of branched amphiphilic peptides that associate with double stranded DNA and promote in vitro transfection of eukaryotic cells. In the present study, we tested a different formulation in which plasmid DNA associates with the surface of preformed 20–30 nm cationic capsules formed through the self-assembly of the two branched amphiphilic peptides. Under these conditions, the negatively charged DNA interacts with the cationic surface of the Branched Amphiphilic Peptide Capsules (BAPCs) through numerous electrostatic interactions generating peptide-DNA complexes with sizes ranging from 50 to 250 nm. The BAPCs-DNA nanoparticles are capable of delivering plasmid DNA of different size into cells in culture, yielding high transfection rates and minimal cytotoxicity. Furthermore, BAPCs were tested for in vivo delivery of a DNA vaccine previously designed to activate immune responses and capable of controlling tumors induced by type 16 human papilloma virus (HPV-16). The BAPCs-DNA nanoparticles enhanced the vaccine-induced antitumor protection and promoted activation of murine dendritic cells without significant toxic effects. These results indicate that branched amphiphilic oligo-peptides nanoparticles represent a new and promising nonviral DNA/gene delivery approach endowing immunomodulatory properties for DNA vaccines.