Since the 2013 Nobel Prize was awarded for the discovery of vesicle trafficking, a subgroup of nanovesicles called exosomes has been driving the research field to a new regime for understanding cellular communication. This exosome-dominated traffic control system has increased understanding of many diseases, including cancer metastasis, diabetes, and HIV. In addition to the important diagnostic role, exosomes are particularly attractive for drug delivery, due to their distinctive properties in cellular information transfer and uptake. Compared to viral and non-viral synthetic systems, the natural, cell-derived exosomes exhibit intrinsic payload and bioavailability. Most importantly, exosomes easily cross biological barriers, obstacles that continue to challenge other drug delivery nanoparticle systems. Recent emerging studies have shown numerous critical roles of exosomes in many biological barriers, including the blood–brain barrier (BBB), blood–cerebrospinal fluid barrier (BCSFB), blood–lymph barrier (BlyB), blood–air barrier (BAB), stromal barrier (SB), blood–labyrinth barrier (BLaB), blood–retinal barrier (BRB), and placental barrier (PB), which opens exciting new possibilities for using exosomes as the delivery platform. However, the systematic reviews summarizing such discoveries are still limited. This review covers state-of-the-art exosome research on crossing several important biological barriers with a focus on the current, accepted models used to explain the mechanisms of barrier crossing, including tight junctions. The potential to design and engineer exosomes to enhance delivery efficacy, leading to future applications in precision medicine and immunotherapy, is discussed.

中文翻译：

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释放外来体的力量以克服药物输送中的生物障碍

自从2013年诺贝尔奖因发现小泡运输而被授予以来，被称为外泌体的纳米小泡亚组一直将研究领域推向一个新的领域，以理解细胞通讯。这种以外泌体为主的交通控制系统已使人们更加了解许多疾病，包括癌症转移，糖尿病和艾滋病毒。除了重要的诊断作用外，由于外来体在细胞信息传递和吸收方面具有独特的特性，因此对于药物的输送特别有吸引力。与病毒和非病毒合成系统相比，天然的细胞来源的外泌体具有内在的有效负载和生物利用度。最重要的是，外泌体很容易越过生物障碍，这些障碍继续挑战其他药物输送纳米颗粒系统。最近的新兴研究表明，外泌体在许多生物屏障中具有许多关键作用，包括血脑屏障（BBB），血脑脊液屏障（BCSFB），血淋巴屏障（BlyB），血气屏障（BAB），基质屏障（SB），血迷宫屏障（BLaB），血视网膜屏障（BRB）和胎盘屏障（PB），这为使用外泌体作为递送平台开辟了令人兴奋的新可能性。但是，总结此类发现的系统评价仍然有限。这篇综述涵盖了跨几个重要的生物障碍的最新外泌体研究，重点是用于解释障碍跨越机制（包括紧密连接）的当前公认模型。设计和工程化外泌体以增强递送功效的潜力，