Abstract
Tracking vaccine components from the site of injection to their destination in lymphatic tissue, and simultaneously monitoring immune effects, sheds light on the influence of vaccine components on particle and immune cell trafficking and therapeutic efficacy. In this study, we create a hybrid particle vaccine platform comprised of porous silicon (pSi) and superparamagnetic iron oxide nanoparticles (SPIONs). The impact of nanoparticle size and mode of presentation on magnetic resonance contrast enhancement are examined. SPION-enhanced relaxivity increased as the core diameter of the nanoparticle increased, while encapsulation of SPIONs within a pSi matrix had only minor effects on T2 and no significant effect on T2* relaxation. Following intravenous injection of single and hybrid particles, there was an increase in negative contrast in the spleen, with changes in contrast being slightly greater for free compared to silicon encapsulated SPIONs. Incubation of bone marrow-derived dendritic cells (BMDC) with pSi microparticles loaded with SPIONs, SIINFEKL peptide, and lipopolysaccharide stimulated immune cell interactions and interferon gamma production in OT-1 TCR transgenic CD8+ T cells. Overall, the hybrid particle platform enabled presentation of a complex payload that was traceable, stimulated functional T cell and BMDC interactions, and resolved in cellular activation of T cells in response to a specific antigen.
Highlights
Cellular uptake of microbes by dendritic cells (DC) is accompanied by engagement of pattern recognition receptors [1,2]
We previously demonstrated that DC incubated with porous silicon particles presenting LPS and antigen are actively engaged by T cells obtained from C57BL/6-Tg(TcraTcrb)
scanning electron microscopy (SEM) images confirm that porous silicon (pSi) microparticles are discoidal in shape with dimensions of 1000 × 400 nm (Figure 1b)
Summary
Cellular uptake of microbes by dendritic cells (DC) is accompanied by engagement of pattern recognition receptors [1,2] Activation of these receptors induces phagocytosis and expression of genes that cause maturation of the cell and activation of anti-microbial events, thereby inducing innate immunity. The stimulated DC have enhanced migration to the draining lymph node and elevated expression of MHC and costimulatory molecules, as well as increased secretion of proinflammatory cytokines. While these early studies relied on ex vivo modification of APC with fluorescent tracers, particle-based vaccines that incorporate contrast agents can be used experimentally or clinically for noninvasive detection by magnetic resonance imaging (MRI) to track migration of particles, or their cell-based carriers, to lymphatic tissue for modulation of immune responses
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