Silica-Based Nanoparticles Targeting Dendritic Cells for Cancer Immunotherapy
BackgroundVaccination is a promising anticancer strategy, but the limited delivery routes and short retention of antigens and immunomodulatory agents are problems that need to be solved in vaccine design. Because silicon nanoparticles have a tunable pore size and high loading capacity, they have been used in a variety of drug delivery systems, but their roles in tumor vaccine and tumor immunotherapy need to be examined.MethodsCD40 mAb was attached to mesoporous silica nanoparticles (MSNs)
... h covalent conjunction, and MSN-CD40/OVA/CpG nanoparticles were examined by Fourier transform-infrared spectroscopy, transmission electron microscopy and nanoparticle analyzer. In vitro functions of nanoparticles were detected by cytotoxicity, cellular uptake, DC maturation, cross-presentation and T cell priming. In vivo functions were monitored by tumor elimination, DC maturation, cross-presentation and T cell activity.ResultsWe encapsulated anti-CD40 monoclonal antibodies, ovalbumin (OVA) antigen, and a toll-like receptor-9 agonist (CpG) in mesoporous silica nanoparticles (MSNs). The resulting MSN-CD40/OVA/CpG nanoparticles were efficiently phagocytized by splenocytes and bone marrow-derived dendritic cells (BMDC). The MSN-CD40/OVA/CpG nanoparticles induced the BMDC to express the costimulatory molecules CD80 and CD86, and release tumor necrosis factor-α. We found that MSN-CD40/OVA/CpG nanoparticles correctly enhanced antigen cross-priming, and stimulated T cell proliferation and interferon γ (IFNγ) production in vitro. In vivo, the MSN-CD40/OVA/CpG nanoparticles strongly increased intracellular IFNγ secretion and its release from OVA257–264 peptide-specific splenocytes into the cell supernatant, induced dendritic cell expression of major histocompatibility complex-II, and stimulated lymphocyte CD80 and CD86 expression. The MSN-CD40/OVA/CpG nanoparticles also inhibited tumor growth, enhanced tumor infiltration of CD8+ and CD4+ T cells, and stimulated IFNγ secretion from splenocytes. In conclusion, we believe these MSN-CD40/OVA/CpG nanoparticles are a promising strategy for improving antigen cross-presentation, cytotoxic T lymphocyte immune activity, and anti-tumor immunotherapy.