Silica-Based Nanoparticles Targeting Dendritic Cells for Cancer Immunotherapy release_ldo4rkihhfdd5ajxfqflptygtm

Abstract

<jats:title>Abstract</jats:title> 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) through 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 OVA<jats:sub>257–264</jats:sub> 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<jats:sup>+</jats:sup> and CD4<jats:sup>+</jats:sup> 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.
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