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 effect in cellulo (IC₅₀ = 2.5 μM). In vivo mouse 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.

炎症与癌症、心血管疾病、感染等一系列疾病相关，蛋白质的磷酸化/去磷酸化修饰在炎症调节中具有重要作用。在这里，我们设计并合成了一种新型的巴西林-Ce纳米粒子（BX-Ce NPs），使用巴西林（已用于心血管疾病的抗炎但治疗窗口窄）和铈（IV），一种具有一般活性的镧系元素催化磷酸酯键的水解，从而赋予 IKKβ 去磷酸化/抗磷酸化作用。我们发现 BX-Ce NP 特异性结合 IKKβ 的 Asn225 和 Lys428，并抑制其 Ser181 磷酸化，从而在细胞中具有明显的抗炎作用（IC ₅₀  = 2.5 μM）。心肌梗死和脓毒症的体内小鼠模型还表明，BX-Ce NP 通过下调 IKKβ 的磷酸化，显着改善实验性脓毒症小鼠的心肌损伤并提高存活率。这些发现为开发用于引导离子干扰疗法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。