Key Laboratory of Molecular Nanostructure and Nanotechnology, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
School of Chemistry and Chemical Engineering, Inner Mongolia University, Inner Mongolia 010021, China.
ACS Appl Mater Interfaces. 2024 Feb 7;16(5):5536-5547. doi: 10.1021/acsami.3c16168. Epub 2024 Jan 24.
Autoimmune hepatitis (AIH) is a severe immune-mediated inflammatory liver disease whose standard of care is immunosuppressive treatment with inevitable undesired outcomes. Macrophage is acknowledged to aggravate liver damage, providing a promising AIH therapeutic target. Accordingly, in this study, a kind of curdlan-decorated fullerene nanoparticle (Cur-F) is fabricated to alleviate immune-mediated hepatic injury for treating AIH via reducing macrophage infiltration in a concanavalin A (Con A)-induced AIH mouse model. After intravenous administration, Cur-F primarily distributes in liver tissues, efficiently eliminates the excessive reactive oxygen species, significantly attenuates oxidative stress, and subsequently suppresses the nuclear factor kappa-B-gene binding (NF-κB) signal pathway, resulting in the lowered production of pro-inflammatory cytokines and the balancing of the immune homeostasis with the prevention of macrophage infiltration in the liver. The regulation of hepatic inflammation contributes to inhibiting inflammatory cytokines-induced hepatocyte apoptosis, decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents and thus ameliorating immune-mediated hepatic injury. Notably, there is no detectable toxicity to the body. Our findings may open up novel avenues for AIH based on curdlan and fullerene materials.
自身免疫性肝炎（AIH）是一种严重的免疫介导的炎症性肝病，其标准治疗方法是免疫抑制治疗，但不可避免地会产生不良后果。巨噬细胞被认为会加重肝损伤，为 AIH 的治疗提供了一个有前途的治疗靶点。因此，在这项研究中，制备了一种葡聚糖修饰的富勒烯纳米粒子（Cur-F），通过减少 ConA 诱导的 AIH 小鼠模型中的巨噬细胞浸润，来减轻免疫介导的肝损伤，从而治疗 AIH。静脉注射后，Cur-F 主要分布在肝组织中，能有效清除过多的活性氧，显著减轻氧化应激，随后抑制核因子 kappa-B-基因结合（NF-κB）信号通路，降低促炎细胞因子的产生，平衡免疫稳态，防止巨噬细胞浸润肝脏。肝脏炎症的调节有助于抑制炎症细胞因子诱导的肝细胞凋亡，降低血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）含量，从而改善免疫介导的肝损伤。值得注意的是，对身体没有可检测到的毒性。我们的研究结果可能为基于葡聚糖和富勒烯材料的 AIH 治疗开辟新的途径。
