Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cells. 2022 Jun 15;11(12):1933. doi: 10.3390/cells11121933.
Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids, and genetic material, playing important roles in intracellular communication. They have remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage-derived EVs to treat Parkinson disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfected ex vivo to express glial-cell-line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that, along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four-month-old transgenic Parkin Q311(X)A mice were treated with EV-GDNF via intranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increases in neuronal survival, and decreases in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administration was detected. Overall, an EV-based approach can provide a versatile and potent therapeutic intervention for PD.
细胞外囊泡 (EVs) 是细胞衍生的纳米颗粒，可促进蛋白质、脂质和遗传物质的运输，在细胞内通讯中发挥重要作用。它们作为非毒性和非免疫原性的纳米载体，具有将药物递送到无法到达的器官和组织（特别是中枢神经系统）的巨大潜力。在此，我们开发了一种基于巨噬细胞衍生 EVs 的新型平台来治疗帕金森病 (PD)。具体而言，我们评估了经自体巨噬细胞转染表达胶质细胞系源性神经营养因子 (GDNF) 后分泌的 EVs 的治疗潜力。从 GDNF 转染的巨噬细胞的条件培养基中收集 EV-GDNF，并对其 GDNF 含量、大小、电荷和 EV 特异性蛋白的表达进行表征。数据显示，与编码的神经营养因子一起，经预转染的巨噬细胞释放的 EV 携带 GDNF 编码 DNA。通过鼻腔内给药，用 EV-GDNF 治疗 4 月龄的转帕金森基因 Q311(X)A 小鼠，并在一年的时间里评估这种治疗干预对运动功能的影响。在接受 EV-GDNF 治疗的 PD 小鼠中，发现运动能力显著改善、神经元存活率增加和神经炎症减少。未检测到 EV-GDNF 给药引起的场外毒性。总的来说，基于 EV 的方法可为 PD 提供一种多功能且有效的治疗干预手段。
