School of Life Sciences , University of Science and Technology of China , Hefei , Anhui 230027 , China.
State Key Laboratory of Physical Chemistry of Solid Surfaces, The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, The Key Laboratory for Chemical Biology of Fujian Province, and iChEM, College of Chemistry and Chemical Engineering , Xiamen University , Xiamen 361005 , China.
ACS Appl Mater Interfaces. 2018 Dec 5;10(48):41197-41206. doi: 10.1021/acsami.8b17474. Epub 2018 Nov 21.
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.
炎症小体是先天免疫系统的关键组成部分，介导了工程纳米材料表现出的大部分炎症反应。氧化铁纳米颗粒（IONP）是一种在临床前和临床环境中广泛接受的纳米颗粒类型，已知会诱导炎症小体的激活，但形态如何影响 IONP 的炎症小体激活特性尚未得到解决。在本报告中，我们合成了具有相同纵横比和相似表面电荷的四种形态不同的 IONP，从而提供了一个评估形态对纳米颗粒引发的生物学效应影响的理想系统。我们表明，形态是 IONP 诱导的 IL-1β释放和细胞焦亡的关键决定因素，八角形和片状 IONP 比立方体形和球形 IONP 表现出显著更高的活性。不同 IONP 的炎症小体激活能力与它们各自诱导细胞内活性氧产生、溶酶体损伤和钾外流的能力相关，这是纳米颗粒促进炎症小体激活的三个众所周知的机制。此外，我们证明 IONP 诱导的 IL-1β释放仅部分由 NLRP3 介导，表明除 NLRP3 之外的炎症小体也参与了 IONP 诱导的炎症小体激活。我们的结果可能对设计用于体内应用的更安全的纳米颗粒具有重要意义。
