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Macrophage activation status determines the internalization of mesoporous silica particles of different sizes: Exploring the role of different pattern recognition receptors
Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
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Number of Authors: 7
2017 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 121, 28-40 p.Article in journal (Refereed) Published
Abstract [en]

Mesoporous silica-based particles are promising candidates for biomedical applications. Here, we address the importance of macrophage activation status for internalization of AMS6 (approx. 200 nm in diameter) versus AMS8 (approx. 2 mu m) mesoporous silica particles and the role of different phagocytosis receptors for particle uptake. To this end, FITC-conjugated silica particles were used. AMS8 were found to be non-cytotoxic both for M-CSF-stimulated (anti-inflammatory) and GM-CSF-stimulated (pro-inflammatory) macrophages, whereas AMS6 exhibited cytotoxicity towards M-CSF-stimulated, but not GMCSF-stimulated macrophages; this toxicity was, however, mitigated in the presence of serum. AMS8 triggered the secretion of pro-inflammatory cytokines in M-CSF-activated cells. Class A scavenger receptor (SR-A) expression was noted in both M-CSF and GM-CSF-stimulated macrophages, although the expression was higher in the former case, and gene silencing of SR-A resulted in a decreased uptake of AMS6 in the absence of serum. GM-CSF-stimulated macrophages expressed higher levels of the mannose receptor CD206 compared to M-CSF-stimulated cells, and uptake of AMS6, but not AMS8, was reduced following the downregulation of CD206 in GM-CSF-stimulated cells; particle uptake was also suppressed by mannan, a competitive ligand. These studies demonstrate that macrophage activation status is an important determinant of particle uptake and provide evidence for a role of different macrophage receptors for cell uptake of silica particles.

Place, publisher, year, edition, pages
2017. Vol. 121, 28-40 p.
Keyword [en]
Silica particles, Human macrophages, Scavenger receptors, mannose receptors
National Category
Biological Sciences Medical Engineering
Identifiers
URN: urn:nbn:se:su:diva-141226DOI: 10.1016/j.biomaterials.2016.12.029ISI: 000393933000003PubMedID: 28063981OAI: oai:DiVA.org:su-141226DiVA: diva2:1089303
Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2017-04-19Bibliographically approved

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Kupferschmidt, Natalia
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CiteExportLink to record
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Citation style
  • apa
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