Non-Functionalized Ultrasmall Silica Nanoparticles Directly and Size-Selectively Activate T Cells.
Rodrigues Faria, Nuno
Passos Bastos, Carlos
Kinrade, Stephen D
American Chemical Society (ACS)
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Vis, B., Hewitt, R., Rodrigues Faria, N., Passos Bastos, C., Chappell, H., Pele, L., Jugdaohsingh, R., et al. (2018). Non-Functionalized Ultrasmall Silica Nanoparticles Directly and Size-Selectively Activate T Cells.. ACS Nano, 12 (11), 10843-10854. https://doi.org/10.1021/acsnano.8b03363
Sub-micron-sized silica nanoparticles, even as small as 10-20 nm in diameter, are well-known for their activation of mononuclear phagocytes. In contrast, the cellular impact of those <10 nm [ i.e., ultrasmall silica nanoparticles (USSN)] is not well-established for any cell type despite anticipated human exposure. Here, we synthesized discrete populations of USSN with volume median diameters between 1.8 to 16 nm and investigated their impact on the mixed cell population of human primary peripheral mononuclear cells. USSN 1.8-7.6 nm in diameter, optimally 3.6-5.1 nm in diameter, induced dose-dependent CD4 and CD8 T-cell activation in terms of cell surface CD25 and CD69 up-regulation at concentrations above 150 μM Sitotal (∼500 nM particles). Induced activation with only ∼2.4 μM particles was (a) equivalent to that observed with typical positive control levels of Staphylococcal enterotoxin B (SEB) and (b) evident in antigen presenting cell-deplete cultures as well as in a pure T-cell line (Jurkat) culture. In the primary mixed-cell population, USSN induced IFN-γ secretion but failed to induce T-cell proliferation or the secretion of IL-2, IL-10, or IL-4. Collectively, these data indicate that USSN initiate activation, with Th1 polarization, of T cells via direct particle-cell interaction. Finally, similarly sized iron hydroxide particles did not induce the expression of T-cell activation markers, indicating some selectivity of the ultrasmall particle type. Given that humans may be exposed to ultrasmall particles and that these materials have emerging bioclinical applications, their off-target immunomodulatory effects via direct T-cell activation should be carefully considered.
T-Lymphocytes, Cells, Cultured, Jurkat Cells, Humans, Silicon Dioxide, Dose-Response Relationship, Drug, Particle Size, Surface Properties, Nanoparticles
Grant number MR/R005699/1
Medical Research Council (MR/R005699/1)
External DOI: https://doi.org/10.1021/acsnano.8b03363
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286424