Macrophage activation status determines the internalization of mesoporous silica particles of different sizes: exploring the role of different pattern recognition receptors

Audrey Gallud, Olesja Bondarenko, Neus Feliu, Natalia Kupferschmidt, Rambabu Atluri, Alfonso Garcia-Bennett, Bengt Fadeel*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    30 Citations (Scopus)

    Abstract

    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 μm) 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 GM-CSF-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.

    Original languageEnglish
    Pages (from-to)28-40
    Number of pages13
    JournalBiomaterials
    Volume121
    DOIs
    Publication statusPublished - Mar 2017

    Keywords

    • Silica particles
    • Human macrophages
    • Scavenger receptors
    • Mannose receptors

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