Graduate School of Pharmaceutical Sciences and School of Pharmacy, Duquesne University, Pittsburgh, PA, USA.
J Control Release. 2022 Mar;343:400-407. doi: 10.1016/j.jconrel.2022.01.045. Epub 2022 Feb 4.
The field of drug delivery has made tremendous advances in increasing the therapeutic potential of a variety of drug candidates spanning from small molecules to large molecular biologics such as nucleic acids, proteins, etc. Extracellular vesicles (EVs) are mediators of intercellular communication and carry a rich cocktail of innate cargo including lipids, proteins and nucleic acids. EVs are a promising class of natural, cell-derived carriers for drug delivery. EVs of particle diameters <200 nm are referred to as small EVs (sEVs) and medium-to-larger particles of diameters >200 nm are referred to as m/lEVs. The m/lEVs naturally incorporate mitochondria during their biogenesis. In this Oration, I will discuss the potential of m/lEVs as carriers for the delivery of healthy and functional mitochondria. Mitochondrial damage and dysfunction play a causal role in multiple pathologies such as neurodegenerative diseases, cardiovascular and metabolic diseases-suggesting that m/lEV-mediated mitochondria delivery can be of broad biomedical significance. A major advantage of harnessing m/lEVs is that the delivered mitochondria are capable of using endogenous mechanisms for repairing the cellular damage. I will highlight the delivery potential of m/lEVs based on the studies we have conducted so far and discuss unaddressed issues towards their development as a novel class of mitochondria carriers.
在提高各种候选药物的治疗潜力方面，药物输送领域取得了巨大进展，这些候选药物涵盖从小分子到核酸、蛋白质等大型生物分子。细胞外囊泡 (EVs) 是细胞间通讯的介质，携带包括脂质、蛋白质和核酸在内的丰富内源性货物。EVs 是一类很有前途的天然、细胞衍生的药物输送载体。粒径 <200nm 的 EVs 被称为小 EVs（sEVs），粒径 >200nm 的中到大颗粒被称为 m/lEVs。m/lEVs 在其生物发生过程中自然整合线粒体。在这篇演讲中，我将讨论 m/lEVs 作为携带健康和功能线粒体的载体的潜力。线粒体损伤和功能障碍在多种病理学中起着因果作用，如神经退行性疾病、心血管和代谢疾病——这表明 m/lEV 介导的线粒体输送具有广泛的生物医学意义。利用 m/lEVs 的一个主要优势是，输送的线粒体能够利用内源性机制修复细胞损伤。我将根据我们迄今为止开展的研究，强调 m/lEVs 的输送潜力，并讨论在将其开发为一类新型线粒体载体方面尚未解决的问题。
