Extracellular vesicles as next-generation therapeutics and biomarkers in amyloidosis: a new frontier

Thanh Huyen Phan, Joanne H. Reed
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Abstract

Nanoparticles hold a great potential for therapeutic targeting due to their ability to improve the stability of encapsulated cargo and promote the transport of cargo across membranes to reach to the target site. Most commercially available nanomedicines are simple synthetic liposomes, however, there are numerous side effects due to their off-target delivery and rapid clearance from the bloodstream. Recently, attention has moved toward extracellular vesicles (EVs)–lipid bilayer enclosed particles released by cells (size ranging from 30 to 10,000 nm in diameter). EVs carry and transport lipids, proteins, and nucleic acids from their parental cells to recipient cells, hence they play a key role in intercellular communication. The ability of EVs to cross biological barriers including the blood brain barrier has generated significant attention to explore them as potential biomarkers and natural drug delivery vehicles for various therapeutics and small molecules. EVs have also been implicated in disease pathogenesis by transmitting pathogenic proteins between cells, making them promising biomarkers for disease diagnosis and monitoring. In this review, we will focus on the potential and challenges of EVs as biomarkers, drug delivery vehicles and next-generation therapeutics. Finally, we will explore misfolded protein disorders, amyloidosis, as a case study for how EVs may contribute to disease pathology and how EVs could be applied in the clinic as diagnostic and prognostic biomarkers of amyloid diseases.
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细胞外囊泡作为淀粉样变性病的新一代疗法和生物标记物:一个新领域
纳米颗粒能够提高封装货物的稳定性,并促进货物跨膜运输到达靶点,因此在靶向治疗方面具有巨大潜力。大多数市售纳米药物都是简单的合成脂质体,但由于其脱靶传输和快速从血液中清除的特性,存在许多副作用。最近,人们开始关注细胞外囊泡 (EV)--细胞释放的脂质双分子层封闭颗粒(直径从 30 纳米到 10,000 纳米不等)。细胞外囊泡携带和运输脂质、蛋白质和核酸,将其从母细胞运送到受体细胞,因此在细胞间通信中发挥着关键作用。EVs 能够穿越包括血脑屏障在内的生物屏障,这引起了人们对其作为潜在生物标记物以及各种治疗药物和小分子天然药物递送载体的极大关注。通过在细胞间传递致病蛋白,EVs 也被认为与疾病的发病机理有关,因此是诊断和监测疾病的有前途的生物标记物。在这篇综述中,我们将重点探讨 EVs 作为生物标记物、给药载体和下一代疗法的潜力和挑战。最后,我们将以折叠错误的蛋白质疾病--淀粉样变性病--为案例,探讨EV如何对疾病病理做出贡献,以及EV如何作为淀粉样变性疾病的诊断和预后生物标记物应用于临床。
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