Brazilin-Ce nanoparticles attenuate inflammation by de/ anti-phosphorylation of IKKβ
Brazilin-Ce nanoparticles attenuate inflammation by de/ anti-phosphorylation of IKKβ
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DOI：
10.1016/j.biomaterials.2023.122466
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发表时间：
2024-01-06
期刊：
影响因子：
14
通讯作者：
Xiang，Yaozu
中科院分区：
文献类型：
--
作者：
Li，Shengxuan;Wang，Kun;Xiang，Yaozu
炎症与癌症、心血管疾病、感染等一系列疾病有关，蛋白的磷酸化/去磷酸化修饰在炎症调节中起重要作用。在这里，我们设计并合成了一种新的巴西- ce纳米颗粒（BX-Ce NPs），使用巴西素来用于心血管疾病的抗炎症，但治疗窗口较窄，以及铈（IV），一种具有催化磷酸酯键水解的一般活性的镧系元素，赋予IKKβ去磷酸化/抗磷酸化。我们发现BX-Ce NPs特异性结合到IKKβ的Asn225和Lys428上，抑制其Ser181的磷酸化，对细胞有明显的抗炎作用（IC50= 2.5 μM）。在小鼠心肌梗死和脓毒症模型中也显示，BX-Ce NPs通过下调IKKβ磷酸化，显著改善实验性脓毒症小鼠的心肌损伤和生存率。这些发现为开发用于引导离子干扰治疗的金属纳米颗粒提供了见解，特别是协同靶向去磷酸化/抗磷酸化作为炎症和相关疾病的有希望的治疗剂。
Inflammation is associated with a series of diseases like cancer, cardiovascular disease and infection, and phosphorylation/dephosphorylation modification of proteins are important in inflammation regulation. Here we designed and synthesized a novel Brazilin-Ce nanoparticle (BX-Ce NPs) using Brazilin, which has been used for anti-inflammation in cardiovascular diseases but with narrow therapeutic window, and Cerium (IV), a lanthanide which has the general activity in catalyzing the hydrolysis of phosphoester bonds, to conferring de/anti-phosphorylation of IKKβ. We found that BX-Ce NPs specifically bound to Asn225 and Lys428 of IKKβ and inhibited its phosphorylation at Ser181, contributing to appreciably anti-inflammatory effectin cellulo(IC50= 2.5 μM).In vivomouse models of myocardial infarction and sepsis also showed that the BX-Ce NPs significantly ameliorated myocardial injury and improved survival in mice with experimental sepsis through downregulating phosphorylation of IKKβ. These findings provided insights for developing metal nanoparticles for guided ion interfere therapy, particularly synergistically target de/anti-phosphorylation as promising therapeutic agents for inflammation and related diseases.