Zhao Xin, Fan Zun, Zhu Chengyang, Zhang Weigang, Qin Lei
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Mater Today Bio. 2023 Jun 24;21:100711. doi: 10.1016/j.mtbio.2023.100711. eCollection 2023 Aug.
Patients with hepatic fibrosis (HF) have a high risk of developing liver cirrhosis and hepatocellular carcinoma, and there is an urgent need for preventive strategies to block this process. Previous studies have found that disordered inflammation and oxidative damage play important roles in HF progression, suggesting two attractive therapeutic targets. Herein, a new kind of bioinspired microcapsules with a core-shell structure is generated using microfluidics. Polydopamine nanoparticles (PDANPs), a synthetic analogue of natural melanin, are embedded in the polymer shell to provide antioxidative properties for these microcapsules. The aqueous core is used to encapsulate ketone body β-hydroxybutyrate (BHB), an energy metabolite recently known to have regulating effects of cellular signals involved in chronic inflammation. In a HF mouse model, the BHB-encapsulated PDANPs-embedded microcapsules (BHB-PDA-MCs) can not only decrease the severity of inflammatory response, but also the level of oxidative stress. As a result, this combinational strategy is demonstrated to prevent the activation of hepatic stellate cells, the accumulation of extracellular matrix, and the damage of hepatic lobules. These findings indicate that BHB-PDA-MCs can be a promising drug delivery system and have a synergistic effect on HF management.
肝纤维化（HF）患者发生肝硬化和肝细胞癌的风险很高，迫切需要采取预防策略来阻断这一进程。先前的研究发现，炎症紊乱和氧化损伤在HF进展中起重要作用，这提示了两个有吸引力的治疗靶点。在此，利用微流控技术制备了一种新型的具有核壳结构的仿生微胶囊。聚多巴胺纳米颗粒（PDANPs）是天然黑色素的合成类似物，被嵌入聚合物壳中，为这些微胶囊提供抗氧化性能。水相核心用于包裹酮体β-羟基丁酸酯（BHB），这是一种最近已知对参与慢性炎症的细胞信号具有调节作用的能量代谢物。在HF小鼠模型中，包裹BHB的嵌入PDANPs的微胶囊（BHB-PDA-MCs）不仅可以降低炎症反应的严重程度，还可以降低氧化应激水平。结果表明，这种联合策略可预防肝星状细胞的激活、细胞外基质的积累以及肝小叶的损伤。这些发现表明，BHB-PDA-MCs可能是一种有前途的药物递送系统，对HF治疗具有协同作用。
