氧化铈(CeO2)纳米球的酶活性有限,阻碍了在催化疗法中的进一步应用。但是它们有一个“氧化开关”,通过增加氧空位来增强它们的催化活性。在这项研究中,根据缺陷工程策略,我们通过将双金属铜(Cu)和铂(Pt)引入CeO2纳米球以增强氧空位,开发了PtCuOX/CeO2-X纳米酶作为高效的SOD/CAT模拟物,尝试结合近红外(NIR)照射来调节骨关节炎(OA)治疗的微环境。不出所料,Cu和Pt提高了CeO2的Ce3+/Ce4+比值,显著增强了氧空位,同时CeO2(111)促进了Cu和Pt的均匀分散。强的金属-载体相互作用协同作用通过降低氧空位形成能赋予PtCuOX/CeO2-X纳米酶高效的SOD/CAT样活性,促进电子转移,中间体的吸附能增加,反应活化能降低。此外,纳米酶具有优异的光热转化效率(55.41%)。Further,PtCuOX/CeO2-X抗氧化系统有效清除细胞内ROS和RNS,受保护的线粒体功能,抑制炎症因子,从而减少软骨细胞凋亡。在体内,实验证明了PtCuOX/CeO2-X的生物安全性及其对OA抑制的有效作用。特别是,NIR辐射进一步增强了效果。机械上,PtCuOX/CeO2-X纳米酶降低ras相关C3肉毒毒素底物1(Rac-1)和p-p65蛋白表达,以及ROS水平通过抑制ROS/Rac-1/核因子κB(NF-κB)信号通路来重塑炎症微环境。这项研究引入了可应用于炎症性疾病的新临床概念和观点。
Cerium oxide (CeO2) nanospheres have limited enzymatic activity that hinders further application in catalytic therapy, but they have an \"oxidation switch\" to enhance their catalytic activity by increasing oxygen vacancies. In this study, according to the defect-engineering strategy, we developed PtCuOX/CeO2-X
nanozymes as highly efficient SOD/CAT mimics by introducing bimetallic copper (Cu) and platinum (Pt) into CeO2 nanospheres to enhance the oxygen vacancies, in an attempt to combine near-infrared (NIR) irradiation to regulate microenvironment for osteoarthritis (OA) therapy. As expected, the Cu and Pt increased the Ce3+/Ce4+ ratio of CeO2 to significantly enhance the oxygen vacancies, and simultaneously CeO2 (111) facilitated the uniform dispersion of Cu and Pt. The strong metal-carrier interaction synergy endowed the PtCuOX/CeO2-X
nanozymes with highly efficient SOD/CAT-like activity by the decreased formation energy of oxygen vacancy, promoted electron transfer, the increased adsorption energy of intermediates, and the decreased reaction activation energy. Besides, the
nanozymes have excellent photothermal conversion efficiency (55.41%). Further, the PtCuOX/CeO2-X antioxidant system effectively scavenged intracellular ROS and RNS, protected mitochondrial function, and inhibited the inflammatory factors, thus reducing chondrocyte apoptosis. In vivo, experiments demonstrated the biosafety of PtCuOX/CeO2-X and its potent effect on OA suppression. In particular, NIR radiation further enhanced the effects. Mechanistically, PtCuOX/CeO2-X
nanozymes reduced ras-related C3 botulinum toxin substrate 1 (Rac-1) and p-p65 protein expression, as well as ROS levels to remodel the inflammatory microenvironment by inhibiting the ROS/Rac-1/nuclear factor kappa-B (NF-κB) signaling pathway. This study introduces new clinical concepts and perspectives that can be applied to inflammatory diseases.