am8b17474_si_001.pdf (664.39 kB)
Impact of Morphology on Iron Oxide Nanoparticles-Induced Inflammasome Activation in Macrophages
journal contribution
posted on 2018-11-06, 00:00 authored by Liu Liu, Rui Sha, Lijiao Yang, Xiaomin Zhao, Yangyang Zhu, Jinhao Gao, Yunjiao Zhang, Long-Ping WenInflammasomes,
a critical component of the innate immune system,
mediate much of the inflammatory response manifested by engineered
nanomaterials. Iron oxide nanoparticles (IONPs), a type of nanoparticles
that have gained widespread acceptance in preclinical and clinical
settings, are known to induce inflammasome activation, but how morphology
affects the inflammasome-activating property of IONPs has not been
addressed. In this report, we have synthesized four morphologically
distinct IONPs having the same aspect ratio and similar surface charge,
thus offering an ideal system to assess the impact of morphology on
nanoparticle-elicited biological effect. We show that morphology was
a critical determinant for IONP-induced IL-1β release and pyroptosis,
with the octapod and plate IONPs exhibiting significantly higher activity
than the cube and sphere IONPs. The inflammasome-activating capacity
of different IONPs correlated with their respective ability to elicit
intracellular reactive oxygen species generation, lysosomal damage,
and potassium efflux, three well-known mechanisms for nanoparticle-facilitated
inflammasome activation. Furthermore, we demonstrate that the release
of IL-1β induced by IONPs was only partly mediated by NLRP3,
suggesting that inflammasomes other than NLRP3 are also involved in IONP-induced inflammasome
activation. Our results may have implications for designing safer
nanoparticles for in vivo applications.
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Keywords
morphologyIONP-induced IL -1β releaseMacrophages InflammasomesIron Oxide Nanoparticles-Induced Inflammasome Activationinflammasome-activating capacityvivo applicationsIL -1βnanoparticle-facilitated inflammasome activationinflammasome-activating propertysurface chargeiron oxide nanoparticlesplate IONPsintracellular reactive oxygen species generationIONP-induced inflammasome activationNLRP 3lysosomal damagesphere IONPspotassium effluxaspect ratioinflammasome activation
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