RESUMEN
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.
Asunto(s)
ADN/administración & dosificación , Técnicas de Transferencia de Gen , Péptidos/química , Plásmidos/administración & dosificación , Tensoactivos/química , Vacunas de ADN/administración & dosificación , Animales , Línea Celular Tumoral , ADN/genética , Células Dendríticas/inmunología , Papillomavirus Humano 16/inmunología , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Nanocápsulas , Neoplasias/inmunología , Neoplasias/prevención & control , Plásmidos/genética , Vacunas de ADN/genética , Vacunas de ADN/inmunologíaRESUMEN
The cause of Alzheimer's disease is still unknown, but the disease is distinctively characterized by the accumulation of ß-amyloid plaques and neurofibrillary tangles in the brain. These features have become the primary focus of much of the research looking for new treatments for the disease, including immunotherapy and vaccines targeting ß-amyloid in the brain. Adverse effects observed in a clinical trial based on the ß-amyloid protein were attributed to the presence of the target antigen and emphasized the relevance of finding safer antigen candidates for active immunization. For this kind of approach, different vaccine formulations using DNA, peptide, and heterologous prime-boost immunization regimens have been proposed. Promising results are expected from different vaccine candidates encompassing B-cell epitopes of the ß-amyloid protein. In addition, recent results indicate that targeting another protein involved in the etiology of the disease has opened new perspectives for the effective prevention of the illness. Collectively, the evidence indicates that the idea of finding an effective vaccine for the control of Alzheimer's disease, although not without challenges, is a possibility.