Jia Ming, Ren Wei, Liu Yan, Wang Chenglong, Zheng Xiu, Zhang Dan, Tan Xiaoqiu, Li Chunhong
Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan646000, China.
National Traditional Chinese Medicine Clinical Research Base and Drug Research Center of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou646000, China.
ACS Appl Mater Interfaces. 2023 Jan 11;15(1):338-353. doi: 10.1021/acsami.2c16458. Epub 2022 Dec 29.
Dysregulation of superoxide anion (O) and hydrogen peroxide (HO) metabolism in the microenvironment of rheumatoid arthritis (RA) drives the feedback loops of TNF-α and IL-1β thereby inducing an inflammatory storm between immune cells and joint tissue cells. Here, we combine nanoscale manganese dioxide (MnO) with microvesicles derived from macrophage (MMV). The former possesses superoxide dismutase (SOD) and catalase (CAT)-like activities that can modulate this imbalance, and we amplify the enzyme-like activities by using the amorphous hollow mesoporous structure and surface modification. The latter is a natural endogenous component with the parent cell-like inflammatory homing ability and a unique function of transmitting information to surrounding and distant cells (″messenger function″), which helps amorphous hollow MnO (H-MnO) nanozymes to cloak in the blood and reach the site of inflammation, where they can not only accumulate in activated macrophages but also pretend to be ″messengers″ that are utilized by fibroblast-like synoviocytes (FLS) and chondrocytes. In addition, we also load dexamethasone sodium phosphate (DSP) for helping the nanozymes work. Messenger nanozyme (MMV-MnO@DSP) inherits the natural properties of MMV and mimics the enzymatic activity of SOD and CAT. It accumulates in activated macrophages to restore the metabolism of O and HO while promoting repolarization and inhibits the feedback loops of TNF-α and IL-1β among macrophages, fibroblast-like synoviocytes, and chondrocytes, leading to anti-rheumatoid arthritis effects in vitro and in vivo.
类风湿关节炎（RA）微环境中超氧阴离子（O）和过氧化氢（HO）代谢失调驱动肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的反馈回路，从而在免疫细胞和关节组织细胞之间引发炎症风暴。在此，我们将纳米级二氧化锰（MnO）与巨噬细胞衍生的微囊泡（MMV）相结合。前者具有超氧化物歧化酶（SOD）和过氧化氢酶（CAT）样活性，可调节这种失衡，并且我们通过使用无定形中空介孔结构和表面修饰来增强酶样活性。后者是一种天然内源性成分，具有类似母细胞的炎症归巢能力以及向周围和远处细胞传递信息的独特功能（“信使功能”），这有助于无定形中空MnO（H-MnO）纳米酶在血液中伪装并到达炎症部位，在那里它们不仅可以在活化的巨噬细胞中积累，还能伪装成被成纤维样滑膜细胞（FLS）和软骨细胞利用的“信使”。此外，我们还负载地塞米松磷酸钠（DSP）以帮助纳米酶发挥作用。信使纳米酶（MMV-MnO@DSP）继承了MMV的天然特性，并模拟SOD和CAT的酶活性。它在活化的巨噬细胞中积累以恢复O和HO的代谢，同时促进极化并抑制巨噬细胞、成纤维样滑膜细胞和软骨细胞之间TNF-α和IL-1β的反馈回路，从而在体外和体内产生抗类风湿关节炎的作用。
