Li Liang, Sun Chunbin, Cai Shanglin, Hang Zhongci, Gao Xiaoyu, Hou Liangxuan, Li Luping, Wu Yawen, Xing Cencan, Du Hongwu
School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China.
Daxing Research Institute, University of Science and Technology Beijing, Beijing 100083, China.
ACS Appl Mater Interfaces. 2025 Apr 23;17(16):23536-23552. doi: 10.1021/acsami.4c22181. Epub 2025 Apr 9.
Neuroinflammation is a key risk factor for cognitive impairment, and microglia are the main drivers. Metformin has been shown to suppress inflammation and reduce microglial activation, protecting neurons from damage. However, its clinical efficacy is limited by low bioavailability and metabolic challenges, especially in terms of precise delivery to specific targets. To overcome this problem, we developed biomimetic microglial nanoparticles (MePN@BM) to enhance the targeted delivery and bioavailability of metformin. Through homologous targeting, the delivery efficiency of drugs in the inflammatory site of Parkinson's disease was enhanced to improve the therapeutic effect. The results showed that MePN@BM effectively delivers metformin to the brain, promotes autophagy, restores mitochondrial membrane potential, and reduces oxidative stress. In a Parkinson's disease (PD) mouse model, MePN@BM improved motor function, repaired dopaminergic neurons, and cleared α-synuclein aggregates. Notably, transcriptome analysis revealed enriched inflammation-related pathways, and immunofluorescence showed that PD mice treated with MePN@BM had higher levels of anti-inflammatory factors and lower levels of pro-inflammatory factors. Therefore, it provides a promising strategy for the treatment of inflammation-mediated motor dysfunction.
神经炎症是认知障碍的关键危险因素，而小胶质细胞是主要驱动因素。已证明二甲双胍可抑制炎症并减少小胶质细胞活化，保护神经元免受损伤。然而，其临床疗效受到低生物利用度和代谢挑战的限制，尤其是在精确递送至特定靶点方面。为克服这一问题，我们开发了仿生小胶质纳米颗粒（MePN@BM）以提高二甲双胍的靶向递送和生物利用度。通过同源靶向，提高了药物在帕金森病炎症部位的递送效率，从而改善治疗效果。结果表明，MePN@BM能有效地将二甲双胍递送至大脑，促进自噬，恢复线粒体膜电位，并降低氧化应激。在帕金森病（PD）小鼠模型中，MePN@BM改善了运动功能，修复了多巴胺能神经元，并清除了α-突触核蛋白聚集体。值得注意的是，转录组分析显示炎症相关通路富集，免疫荧光显示用MePN@BM治疗的PD小鼠具有较高水平的抗炎因子和较低水平的促炎因子。因此，它为治疗炎症介导的运动功能障碍提供了一种有前景的策略。
