Factors affecting T cell responses induced by fully synthetic glyco-gold-nanoparticles

Abstract

We have synthesized and characterized nearly monodisperse and highly pure gold nanoparticles (2 and 5 nm) coated with non-immunoactive mono-and disaccharides, modelled after the capsular polysaccharide of serogroup A of the Neisseria meningitidis bacterium. We have used them to test their ability to induce immune cell responses as a consequence of their multivalency. The results indicate that they are indeed immunoactive and that immunoactivity is strongly dependent on size, and larger, 5 nm nanoparticles perform far better than smaller, 2 nm ones. Immune response (activation of macrophages) initiates with the whole nanoparticle recognition by the surface of antigen-presenting cells, independent of the saccharide oligomerization (or charge) on the nanoparticle surface. The induction of T cell proliferation and the increase of IL-2 levels, a consequence of the expression of MHC II involved in antigen presentation, require the presence of a disaccharide on the nanoparticle, not just a monosaccharide. A possible explanation is that, at this stage, the saccharides are detached from the gold surface. These results may provide leads for designing new saccharide-based, nanoparticle-conjugate vaccines.

Effective Targeting of DC-SIGN by α-Fucosylamide Functionalized Gold Nanoparticles

“…In this context, it may be worth noting that AuNPs displaying ManNAc mono-and di-saccharides 19 or galactofuranose 20 have been reported to induce significant activation of antigen presenting cells. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 and it was directly proportional to the amount of N-fucosylamide present on the AuNPs (Figure 4b).…”

“…Indeed, some recent studies indicate that even simple monosaccharides can lead to selective nanoparticle recognition and uptake by immune system cells. [19][20] We therefore synthesized gold nanoparticles (AuNPs) functionalized with multiple copies of 1a and measured their ability to interact with DC-SIGN on human DCs and to trigger cellular responses following interaction. AuNPs represent an accessible platform for multivalent presentation.…”

“…21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 Flow cytometry analysis of DC surface molecules and cytokine production. Suspensions of 100 µL immature DCs (1.10 6 cells/mL) were stimulated by addition of AuNPs (1 µg/mL) for [16][17][18][19][20] hours at 37°C in the presence of 5% CO 2 . 10 ng/mL LPS (E. coli, Sigma-Aldrich) served as a control.…”

Efecto inmunomodulador de nanopartículas usadas en nanomedicina

“…Estudios recientes hallaron que tanto los macrófagos como los neutró-filos humanos internalizan las AuNP lo que aumenta la producción intracelular de ROS (62,63). También se ha demostrado que las AuNP pueden iniciar una respuesta inflamatoria mediante la activación de macrófagos tanto in vitro como in vivo (64). Uno de esos estudios halló que AuNP de 40 nm aumentan no solo la hiperreactividad de las vías respiratorias, sino también el número de neutrófilos y macrófagos en ratones sensibilizados (65).…”

Between the Bioactive Extracts of Edible Mushrooms and Pharmacologically Important Nanoparticles: Need for the Investigation of a Synergistic Combination - A Mini Review

“…As already mentioned, nanoparticles have been shown to influence T-cell proliferation, typically through an effect on antigen-presenting cells, leading to an enhanced T-cell stimulatory capacity [103][104][105][106][107].…”