Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Molecular Medicine Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Sci Adv. 2024 Apr 5;10(14):eadl3406. doi: 10.1126/sciadv.adl3406. Epub 2024 Apr 3.
Amyloid aggregation of α-synuclein (αSN) protein amplifies the pathogenesis of neurodegenerative diseases (NDs) such as Parkinson's disease (PD). Consequently, blocking aggregation or redirecting self-assembly to less toxic aggregates could be therapeutic. Here, we improve brain-specific nanocarriers using a hybrid of exosomes (Ex) from human umbilical cord mesenchymal stem cells (hUC MSCs) and nanoliposomes containing baicalein (Ex-NLP-Ba) and oleuropein (Ex-NLP-Ole). The hybrids contained both lipid membranes, Ex proteins, and baicalein or oleuropein. Fluorescence resonance energy transfer analysis confirmed their proper integration. The hybrids reduced the extent of αSN fibrillation and interfered with secondary nucleation and disaggregation. They not only reduced αSN pathogenicity but also enhanced drug internalization into cells, surpassing the efficacy of NLP alone, and also crossed the blood-brain barrier in a cellular model. We conclude that Ex can be successfully extracted and efficiently merged with NLPs while retaining its original properties, demonstrating great potential as a theranostic drug delivery vehicle against NDs like PD.
α-突触核蛋白（αSN）的淀粉样聚集加剧了神经退行性疾病（NDs）的发病机制，如帕金森病（PD）。因此，阻止聚集或重新引导自组装成毒性较低的聚集体可能具有治疗作用。在这里，我们使用人脐带间充质干细胞（hUC MSCs）来源的外泌体（Ex）与含有黄芩素（Ex-NLP-Ba）和橄榄苦苷（Ex-NLP-Ole）的纳米脂质体的混合物来改进脑特异性纳米载体。该混合物包含脂质膜、Ex 蛋白以及黄芩素或橄榄苦苷。荧光共振能量转移分析证实了它们的适当整合。该混合物减少了 αSN 纤维的形成程度，并干扰了二级成核和解聚。它们不仅降低了 αSN 的致病性，而且还增强了药物向细胞内的内化，超过了单独使用 NLP 的效果，并且在细胞模型中也穿过了血脑屏障。我们得出结论，Ex 可以成功提取并有效地与 NLPs 融合，同时保留其原始特性，这表明其作为治疗神经退行性疾病（如 PD）的药物递送载体具有很大的潜力。
