Gene delivery and immunomodulatory effects of plasmid DNA associated with Branched Amphiphilic Peptide Capsules.
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 20-30nm 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 250nm. 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.
Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA; Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506-3902, USA.
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Avila
Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
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Aps
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506-3902, USA.
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Ploscariu
Department of Molecular Biosciences, Kansas University, Lawrence, KS 66045, USA; Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506-3902, USA.
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Sukthankar
Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502, USA.
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Guo
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506-3902, USA.
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Wilkinson
Department of General Biology, Federal University of Viçosa, Viçosa, MG 36570-900, Brazil.
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Games
Faculty of Materials Science and Engineering, Warsaw University of Technology, Warsaw 02-507, Poland.
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Szoszkiewicz
Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
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Alves
Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
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Diniz
Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502, USA.
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Fang
Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
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Ferreira
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, KS 66506-3902, USA. Electronic address: jtomich@ksu.edu.
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Tomich
D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D018014:Gene Transfer Techniques; D052162:Human papillomavirus 16 / Q000276:immunology; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D053769:Nanocapsules; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D013501:Surface-Active Agents / Q000737:chemistry*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
D053769:Nanocapsules; D010455:Peptides; D013501:Surface-Active Agents; D019444:Vaccines, DNA; D004247:DNA
Anti-cancer vaccine; BAPCs; Biocompatible material; Cationic branched peptides; DNA vaccine; HPV; In vivo gene delivery; Peptide-DNA interactions