Impact of Morphology on Iron Oxide Nanoparticles-Induced Inflammasome Activation in Macrophages

Abstract

Inflammasomes, 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.

Enhancing Chemotherapy of p53‐Mutated Cancer through Ubiquitination‐Dependent Proteasomal Degradation of Mutant p53 Proteins by Engineered ZnFe‐4 Nanoparticles

“…Zn and Fe were quantitated with ICP-MS after dissolving them in boiling HNO 3 for 1 h. Fe 3 O 4 was synthesized by following the previous publication. [46] Cell Lines and Culture Conditions: ES-2, BT-549, and BxPC3 were grown in RPMI 1640 medium with 10% FBS. MDA-MB-231, MIA PaCa-2, A549, Hela, APRE-19, and H1299 were grown in DMEM medium with 10% FBS.…”

Engineered Nanomaterials and Type I Allergic Hypersensitivity Reactions

“…Specifically, using 4 different shapes of iron oxide nanoparticles (IONPs), the authors have demonstrated that exposure to the ocatpod and plate-shaped IONPs was associated with increased release of IL-1β release and more cell pyroptosis when compared to the sphere and cube nanoparticles. It has been also found in the same study that activation of the inflammasome by the iron oxide nanoparticles was only partially mediated by NLRP3 (51). Such findings indicate that the same ENMs may induce activation of the inflammasome through multiple receptors/biological targets.…”

Superparamagnetic iron oxide nanoparticles promote ferroptosis of ischemic cardiomyocytes

“…Our in vitro experiment showed that SPION significantly increased oxidative stress damage to overactivate autophagy and endoplasmic reticulum stress, eventually resulting in cardiomyocyte apoptosis 12 . Furthermore, SPION could elicit IL‐1βrelease and pyroptosis in macrophages, especially with the octapod and plate morphology 16 . Notably, it has been recently reported that sorafenib or cisplatin assembled into nano‐devices containing SPION, which are phagocytized by tumour cells and degraded into free divalent iron to accelerate Fenton reaction, leading to the lipid peroxidation burst to promote ferroptosis of tumour cells 17,18 …”