Surface modifications of silica nanoparticles are crucial for their inert versus proinflammatory and immunomodulatory properties

二氧化硅纳米粒子的表面改性对于其惰性、促炎和免疫调节特性至关重要

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作者:Viviana Marzaioli, Juan Antonio Aguilar-Pimentel, Ingrid Weichenmeier, Georg Luxenhofer, Martin Wiemann, Robert Landsiedel, Wendel Wohlleben, Stefanie Eiden, Martin Mempel, Heidrun Behrendt, Carsten Schmidt-Weber, Jan Gutermuth, Francesca Alessandrini

Background

Silica (SiO&sub2;) nanoparticles (NPs) are widely used in diverse industrial and biomedical applications. Their applicability depends on surface modifications, which can limit potential health problems.

Conclusion

Our data suggest that amino and phosphate surface modifications, but not polyethylene glycol (PEG), mitigate the proinflammatory and immunomodulatory effect of SiO&sub2; NPs in allergic airway inflammation, paving the way for new strategies in the production of nanomaterials with lower health impact for humans.

Methods

Mice were sensitized by five repetitive intraperitoneal injections of ovalbumin/aluminum hydroxide (1 μg) over 42 days, then intratracheally instilled with plain or modified SiO&sub2; NPs (50 μg/mouse), and subsequently aerosol challenged for 20 minutes with ovalbumin. One or 5 days later, allergic inflammation was evaluated by cell differentiation of bronchoalveolar lavage fluid, lung function and gene expression and histopathology, as well as electron and confocal microscopy of pulmonary tissue.

Objective

To assess the potential impact of SiO&sub2; NP exposure and NPs chemical modifications in allergic airway inflammation.

Results

Plain SiO&sub2; NPs induced proinflammatory and immunomodulatory effects in vivo, highlighted by enhanced infiltration of inflammatory cells in the bronchoalveolar lavage fluid, induction of a pulmonary T helper type 2 (Th2) cytokine pattern, differentiation of type 2 macrophages, and by morphological changes in the lung of sensitized mice. These effects were dramatically attenuated using surface-functionalized NPs with amino and phosphate groups, but not with polyethylene glycol. The role of macrophages in taking up SiO&sub2; NPs was confirmed by flow cytometry, confocal microscopy, and gene expression analysis.

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