期刊
CURRENT MEDICINAL CHEMISTRY
卷 21, 期 16, 页码 1898-1909出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867321666131129114022
关键词
Dendritic cells; phosphorus dendrimers; nanoparticle; HIV; peptide; vaccine
资金
- EuroNanoMed DENPEPTHIV [PS09/02669]
- COST action [TD0802]
- Red Tematica de Investigacion Cooperativa Sanitaria ISCIII [RED RIS RD06/0006/0035, RD12-0017-0037]
- Fondo de Investigacion Sanitaria (INTRASALUD) [PS09/02029]
- INDISNET [S-2011-BMD2332]
- FIPSE by MAMF
- Spanish MICINN through the Ramon y Cajal [RYC-2009-05486]
- Project DENPEPTHIV [1/EuroNanoMed/2010]
- National Centre of Research and Development of Poland
Aims: The objective was to study if cationic phosphorus dendrimers can be used as DC-based vaccine or adjuvant in anti-HIV-1 vaccine development when associated with HIV-1 derived peptides. Materials & Methods: The HIV-derived peptides uptake in DC and the phenotype of iDC and mDC were studied using Flow Cytometry analysis. Migration of mDC was evaluated by an in vitro chemotaxis assay. Allogenic T-cells proliferative response induced by DC was studied using Flow Cytometry assays. Cytokines production was analysed by Diaclon DIAplex Th1/Th2/Inflammation kit. Results: All phosphorus dendrimers showed the ability to deliver HIV-derived peptides in DC. The phosphorus dendrimers from second and third generations induced important changes in phenotype. Moreover, the treatment of mDC with the second generation dendrimer and derivated dendriplexes modified cellular migratory properties, altered their capacity to stimulate allogenic naive T cells in vitro and impeded the production of pro-inflammatory cytokines. Conclusions: The phosphorus dendrimers cannot be used as vaccines because they would not have the ability to induce an immune response. The cationic phosphorus dendrimers associated with HIV-derived peptides have the ability to deliver peptides as non-viral vectors. However, there are other potential therapeutic applications of these compounds, for instance as topical anti-inflammatory agents, as compounds for allograft rejection or autoimmune diseases and as agents inducing specific tolerance with antigen-loaded DC against allergy reaction. Nevertheless, these applications need to be evaluated.
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