Impact Of Morphology On Iron Oxide Nanoparticles-Induced Inflammasome Activation In Macrophages

Inflammasomes,the critical component of the innate immune system,mediate the inflammatory response induced by exogenous and endogenous activators,and played a key role in the body against pathogens infection.Among the various inflammasomes,the NLRP3 inflammasome is the most studied.Many studies have shown that many nanomaterials can also cause the inflammasome activation.The activation of NLRP3 inflammasome recruits and activates pro-inflammatory caspase-1 which promotes the cleavage and maturation of pro-IL-1?.NLRP3 inflammasome activation also leads to a proinflammatory form of programmed cell death known as pyroptosis.Iron oxide nanomaterials is a kind of high-quality magnetic material,its unique physical and chemical properties make it widely used in biomedical field.At the same time in the development and application of nanomaterials,their biological safety is one of the key factors we need to take into consideration.Now researchers can obtain nanomaterials with good performance and high biocompatibility by changing their size,surface modification and other factors.Recently studies show that iron oxide nanomaterials can cause inflammatory response in cell and animal level,eventually release inflammatory cytokines.However,none of the reports have addressed the issue of morphological impact on IONP-induced inflammasome activation.In this work,we have synthesized four types of IONPs with different morphologies,namely,octapod,plate,cube,and sphere,respectively.These IONPs had nearly the same aspect ratio and similar surface charge,thus giving us an excellent system to evaluate the impact of particle morphology on the capacity of IONPs to activate inflammasomes.We revealed that morphology indeed matters,as significant difference in inflammasome activation activity was observed for these nanoparticles,with the octapod and plate IONPs exhibiting significantly higher inflammasome-activating activity than the cube and sphere IONPs.We also showed that the inflammasome-activating capacity of different IONPs correlated with their respective ability to elicit intracellular ROS generation,lysosomal damage,and potassium efflux,three known mechanisms for nanoparticle-facilitated inflammasome activation.Finally,we demonstrated that the inflammasome activation induced by IONPs was only partially mediated by NLRP3,suggesting that inflammasomes other than NLRP3 also played an important role in IONP-induced IL-1? release and pyroptosis.Iron oxide nanomaterials have immeasurably application prospects,developing high biocompatibility of nanomaterials is in urgency,so we need to make biological safety evaluation on nanomaterials.This study firstly proposed the morphology of iron oxide nanomaterials influences on its safety,which provide a significant guide in designing in vivo used iron oxide nanomaterials.