Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-Constructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, People's Republic of China.
Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China.
J Nanobiotechnology. 2024 Aug 18;22(1):491. doi: 10.1186/s12951-024-02678-z.
Cerium oxide (CeO) 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 PtCuO/CeO nanozymes as highly efficient SOD/CAT mimics by introducing bimetallic copper (Cu) and platinum (Pt) into CeO 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 Ce/Ce ratio of CeO to significantly enhance the oxygen vacancies, and simultaneously CeO (111) facilitated the uniform dispersion of Cu and Pt. The strong metal-carrier interaction synergy endowed the PtCuO/CeO 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 PtCuO/CeO 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 PtCuO/CeO and its potent effect on OA suppression. In particular, NIR radiation further enhanced the effects. Mechanistically, PtCuO/CeO 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.
氧化铈（CeO）纳米球的酶活性有限，这阻碍了其在催化治疗中的进一步应用，但它们具有“氧化开关”，可以通过增加氧空位来增强其催化活性。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 CeO 纳米球中，开发了 PtCuO/CeO 纳米酶作为高效的 SOD/CAT 模拟物，以增强氧空位，试图结合近红外（NIR）照射来调节骨关节炎（OA）治疗的微环境。不出所料，Cu 和 Pt 增加了 CeO 的 Ce/Ce 比值，显著增强了氧空位，同时 CeO（111）促进了 Cu 和 Pt 的均匀分散。强金属载体相互作用协同作用赋予了 PtCuO/CeO 纳米酶高效的 SOD/CAT 样活性，其方法是降低氧空位的形成能、促进电子转移、增加中间体的吸附能以及降低反应活化能。此外，纳米酶具有优异的光热转换效率（55.41%）。进一步，PtCuO/CeO 抗氧化系统有效清除了细胞内的 ROS 和 RNS，保护了线粒体功能，并抑制了炎症因子，从而减少了软骨细胞凋亡。在体内实验中，实验证明了 PtCuO/CeO 的生物安全性及其对 OA 抑制的有效作用。特别是，NIR 辐射进一步增强了这些效果。从机制上讲，PtCuO/CeO 纳米酶通过抑制 ROS/Rac-1/核因子 kappa-B（NF-κB）信号通路，降低 ras 相关 C3 肉毒杆菌毒素底物 1（Rac-1）和 p-p65 蛋白表达以及 ROS 水平，重塑炎症微环境。这项研究引入了新的临床概念和观点，可应用于炎症性疾病。
