四川大学林云锋等研究人员合作利用抗菌核酸负载的类外泌体纳米囊泡，通过口服途径靶向调节肠道菌群改善帕金森病。相关论文于2024年10月24日在线发表在《科学通报》杂志上。

研究人员表示，帕金森病（PD）是最常见的神经退行性疾病之一，通常伴随运动和非运动症状，严重威胁健康和生活质量。由于现有药物只能缓解症状而无法阻止疾病进展，因此迫切需要新药。微生物-肠-脑轴（MGBA）与PD的发生和发展密切相关，是一个有效的治疗靶点。四面体框架核酸（tFNA）可以调节微生物组和免疫调节。然而，这种核酸纳米结构对酸非常敏感，这阻碍了这一有前景的方法。

因此，研究人员从姜中制备了耐酸的类外泌体纳米囊泡（Exo@tac），并用抗菌肽（AMP）修饰tFNA。研究人员验证了Exo@tac在体外调节与微生物-肠-脑轴相关的肠道细菌，并在口服给药时显著改善了小鼠的PD症状。微生物群谱分析证实，Exo@tac使PD小鼠模型的肠道菌群组成正常化。

该研究提出了一种新策略用于PD药物的开发和核酸纳米药物的创新递送。

附：英文原文

Title: Targeting modulation of intestinal flora through oral route by an antimicrobial nucleic acid-loaded exosome-like nanovesicles to improve Parkinson’s disease

Author: Xiao Yang b, Yunfeng Lin a

Issue&Volume: 2024/10/24

Abstract: Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases. It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life. Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression. The microbiota-gut-brain axis (MGBA) is closely associated with the occurrence and development of PD and is an effective therapeutic target. Tetrahedral framework nucleic acids (tFNAs) can modulate the microbiome and immune regulation. However, such nucleic acid nanostructures are very sensitive to acids which hinders this promising approach. Therefore, we prepared exosome-like nanovesicles (Exo@tac) from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides (AMP). We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally. Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD. Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.

DOI: 10.1016/j.scib.2024.10.027

Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927324007710