Yang Dan, Wang Rong, Zhao Lei, Xu Ye, Zhu Yufeng, Zhang Jingyan, Zhou Zhiguo, Sun Yun, Yang Shiping, Yang Hong, Wang Wu
Department of Radiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai, 200234, China.
Mater Today Bio. 2025 Mar 25;32:101705. doi: 10.1016/j.mtbio.2025.101705. eCollection 2025 Jun.
Inflammatory bowel disease (IBD) is characterized by excessive generation of reactive oxygen species and reactive nitrogen species (RONS) within the pro-inflammatory microenvironment. Conventional treatments often have serious side effects, making IBD management challenging. Here, a new cerium cluster, Ce12, with a formula of [Ce( -O)( -OH)( -OH)(ADA)]∙3HO∙3CHCN (ADA = 1-adamantanecarboxylate) was prepared and capped with β-cyclodextrin (β-CD) through self-assembly process involving the adamantane moiety of Ce12 and β-CD, resulting in Ce12@CD nanoparticles (NPs). Ce12@CD NPs, with good stability and biocompatibility, exhibit excellent reactive RONS scavenging activities due to the presence of a fraction of Ce ions, offering potential for treating inflammatory diseases. Treatment significantly alleviated body weight loss, colon length reduction, and pathological injury of colon in mice with dextran sodium sulfate (DSS)-elicited colitis, thereby repairing the intestinal mucosal barrier and reducing inflammation. RNA sequence analysis revealed that the therapeutic effects of Ce12@CD NPs are highly correlated with IL-17 and TNF signaling pathways, thereby reducing inflammatory factors such as IL-1β and TNF-α, and alleviating intestinal inflammation. Additionally, Ce12@CD NPs successfully modulated DSS-induced gut microbiota imbalances. This work highlights the unique catalytic activity of Ce12@CD NPs in removing RONS and mimicking biological enzymes, showcasing their potential therapeutic applications for inflammatory disorders.
炎症性肠病（IBD）的特征是在促炎微环境中活性氧和活性氮物质（RONS）过度生成。传统治疗往往有严重的副作用，这使得IBD的管理具有挑战性。在此，制备了一种新的铈簇Ce12，其化学式为[Ce(-O)(-OH)(-OH)(ADA)]∙3H₂O∙3CH₃CN（ADA = 1-金刚烷羧酸盐），并通过涉及Ce12的金刚烷部分和β-环糊精（β-CD）的自组装过程用β-环糊精进行封端，得到Ce12@CD纳米颗粒（NPs）。Ce12@CD NPs具有良好的稳定性和生物相容性，由于存在一部分铈离子而表现出优异的清除活性RONS的能力，为治疗炎症性疾病提供了潜力。治疗显著减轻了葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠的体重减轻、结肠长度缩短和结肠病理损伤，从而修复肠道黏膜屏障并减轻炎症。RNA序列分析表明，Ce12@CD NPs的治疗效果与IL-17和TNF信号通路高度相关，从而减少了如IL-1β和TNF-α等炎症因子，并减轻了肠道炎症。此外，Ce12@CD NPs成功调节了DSS诱导的肠道微生物群失衡。这项工作突出了Ce12@CD NPs在清除RONS和模拟生物酶方面的独特催化活性，展示了它们在炎症性疾病治疗中的潜在应用。
