FedExosomes: Engineering Therapeutic Biological Nanoparticles that Truly Deliver.
FedExosomes: Engineering Therapeutic Biological Nanoparticles that Truly Deliver.
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联邦交易体：真正提供的工程治疗生物纳米颗粒。
DOI：
10.3390/ph6050659
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Leonard JN
中科院分区：
文献类型：
--
作者：
Marcus ME;Leonard JN
细胞间通讯的许多方面是通过分泌和随后的受体介导的生物分子种类（包括细胞因子、趋化因子甚至代谢物）的检测来“发送”和“接收”信息包来介导的。最近的证据已经建立了一种新的细胞间通讯方式，通过这种方式，生物分子物种通过细胞外脂质囊泡在细胞之间交换。一类特别重要的细胞外囊泡是外来体，其是通常应用于直径约30-200 nm的生物纳米囊泡的术语。外泌体通过内体的内陷形成以包封细胞质内容物，并且在这些多泡内体与细胞表面融合后，外泌体被释放到细胞外空间并在细胞之间转运mRNA、微小RNA（miRNA）和蛋白质。重要的是，外泌体介导的此类货物分子的递送导致受体细胞的功能调节，并且此类调节足以有效地调节体内疾病过程。生物分子的这种功能性递送可能表明外来体利用天然机制（例如，用于内化和运输），其可以通过使用外来体来利用以递送外源RNA用于治疗应用。一个互补的观点是，了解外泌体介导的运输机制可以为“逆向工程”这种机制提供机会，以改善合成递送载体的性能。在这篇综述中，我们总结了利用外泌体进行治疗性RNA递送的最新进展，讨论了工程外泌体克服递送挑战和建立强大技术平台的潜力，并描述了利用外泌体作为RNA递送载体的潜在挑战和优势。
Many aspects of intercellular communication are mediated through “sending” and “receiving” packets of information via the secretion and subsequent receptor-mediated detection of biomolecular species including cytokines, chemokines, and even metabolites. Recent evidence has now established a new modality of intercellular communication through which biomolecular species are exchanged between cells via extracellular lipid vesicles. A particularly important class of extracellular vesicles is exosomes, which is a term generally applied to biological nanovesicles ~30–200 nm in diameter. Exosomes form through invagination of endosomes to encapsulate cytoplasmic contents, and upon fusion of these multivesicular endosomes to the cell surface, exosomes are released to the extracellular space and transport mRNA, microRNA (miRNA) and proteins between cells. Importantly, exosome-mediated delivery of such cargo molecules results in functional modulation of the recipient cell, and such modulation is sufficiently potent to modulate disease processes in vivo. It is possible that such functional delivery of biomolecules indicates that exosomes utilize native mechanisms (e.g., for internalization and trafficking) that may be harnessed by using exosomes to deliver exogenous RNA for therapeutic applications. A complementary perspective is that understanding the mechanisms of exosome-mediated transport may provide opportunities for “reverse engineering” such mechanisms to improve the performance of synthetic delivery vehicles. In this review, we summarize recent progress in harnessing exosomes for therapeutic RNA delivery, discuss the potential for engineering exosomes to overcome delivery challenges and establish robust technology platforms, and describe both potential challenges and advantages of utilizing exosomes as RNA delivery vehicles.