Lin Jun, Dong Liang, Liu Yi-Ming, Hu Yi, Jiang Chen, Liu Ke, Liu Liu, Song Yong-Hong, Sun Mei, Xiang Xing-Cheng, Qu Kun, Lu Yang, Wen Long-Ping, Yu Shu-Hong
Department of Neurosurgery, The First Affiliated Hospital of USTC, School of Basic Medical Sciences, Division of Molecular Medicine, Department of Chemistry, Institute of Biomimetic Materials & Chemistry, Division of Nanomaterials & Chemistry, Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China.
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.
Natl Sci Rev. 2023 Jun 26;10(8):nwad179. doi: 10.1093/nsr/nwad179. eCollection 2023 Aug.
Activation of inflammasomes-immune system receptor sensor complexes that selectively activate inflammatory responses-has been associated with diverse human diseases, and many nanomedicine studies have reported that structurally and chemically diverse inorganic nanomaterials cause excessive inflammasome activation. Here, in stark contrast to reports of other inorganic nanomaterials, we find that nickel-cobalt alloy magnetic nanocrystals (NiCo NCs) actually inhibit activation of NLRP3, NLRC4 and AIM2 inflammasomes. We show that NiCo NCs disrupt the canonical inflammasome ASC speck formation process by downregulating the lncRNA , and experimentally confirm that the entry of NiCo NCs into cells is required for the observed inhibition of inflammasome activation. Furthermore, we find that NiCo NCs inhibit neutrophil recruitment in an acute peritonitis mouse model and relieve symptoms in a colitis mouse model, again by inhibiting inflammasome activation. Beyond demonstrating a highly surprising and apparently therapeutic impact for an inorganic nanomaterial on inflammatory responses, our work suggests that nickel- and cobalt-containing nanomaterials may offer an opportunity to design anti-inflammatory nanomedicines for the therapeutics of macrophage-mediated diseases.
炎性小体（即选择性激活炎症反应的免疫系统受体传感复合物）的激活与多种人类疾病相关，许多纳米医学研究报告称，结构和化学性质各异的无机纳米材料会导致炎性小体过度激活。在此，与其他无机纳米材料的报道形成鲜明对比的是，我们发现镍钴合金磁性纳米晶体（NiCo NCs）实际上会抑制NLRP3、NLRC4和AIM2炎性小体的激活。我们表明，NiCo NCs通过下调lncRNA破坏经典炎性小体ASC斑点形成过程，并通过实验证实观察到的炎性小体激活抑制需要NiCo NCs进入细胞。此外，我们发现NiCo NCs在急性腹膜炎小鼠模型中抑制中性粒细胞募集，并在结肠炎小鼠模型中缓解症状，同样是通过抑制炎性小体激活。除了证明一种无机纳米材料对炎症反应具有高度惊人且明显的治疗作用外，我们的工作还表明，含镍和钴的纳米材料可能为设计用于治疗巨噬细胞介导疾病的抗炎纳米药物提供机会。
