Dept. Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
HansaBioMed OU Tallinn, Estonia and Exosomics Siena S.p.A, Siena, Italy.
Pharmacol Res. 2016 Sep;111:487-500. doi: 10.1016/j.phrs.2016.07.006. Epub 2016 Jul 6.
Exosomes are naturally secreted nanovesicles that have recently aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. These 30-100nm sized vesicles are released from the cells into the extracellular space and ultimately into biofluids in a tightly regulated way. Their molecular composition reflects their cells of origin, may confer specific cell or tissue tropism and underlines their biological activity. Exosomes and other extracellular vesicles (EVs) carry specific sets of proteins, nucleic acids (DNA, mRNA and regulatory RNAs), lipids and metabolites that represent an appealing source of novel noninvasive markers through biofluid biopsies. Exosome-shuttled molecules maintain their biological activity and are capable of modulating and reprogramming recipient cells. This multi-faceted nature of exosomes hold great promise for improving cancer treatment featuring them as novel diagnostic sensors as well as therapeutic effectors and drug delivery vectors. Natural biological activity including the therapeutic payload and targeting behavior of EVs can be tuned via genetic and chemical engineering. In this review we describe the properties that EVs share with conventional synthetic nanoparticles, including size, liposome-like membrane bilayer with customizable surface, and multifunctional capacity. We also highlight unique characteristics of EVs, which possibly allow them to circumvent some limitations of synthetic nanoparticle systems and facilitate clinical translation. The latter are in particular correlated with their innate stability, ability to cross biological barriers, efficiently deliver bioactive cargos or evade immune recognition. Furthermore, we discuss the potential roles for EVs in diagnostics and theranostics, and highlight the challenges that still need to be overcome before EVs can be applied to routine clinical practice.
外泌体是天然分泌的纳米囊泡,由于其在几乎所有生理和病理过程中的细胞间通讯中的作用,最近在科学界和临床界引起了极大的兴趣。这些 30-100nm 大小的囊泡以严格调控的方式从细胞释放到细胞外空间,并最终进入生物体液。它们的分子组成反映了它们的起源细胞,可以赋予特定的细胞或组织趋向性,并强调它们的生物学活性。外泌体和其他细胞外囊泡 (EVs) 携带特定的蛋白质、核酸 (DNA、mRNA 和调节 RNA)、脂质和代谢物,这些物质代表了通过生物体液活检获得新型非侵入性标志物的有吸引力的来源。外泌体转运的分子保持其生物活性,并能够调节和重编程受体细胞。外泌体的这种多方面特性为改善癌症治疗提供了很大的希望,使其成为新型诊断传感器以及治疗效应器和药物递送载体。通过遗传和化学工程,可以调整 EV 的天然生物活性,包括治疗有效载荷和靶向行为。在这篇综述中,我们描述了 EVs 与传统合成纳米颗粒共享的特性,包括大小、具有可定制表面的类脂质体双层膜和多功能能力。我们还强调了 EVs 的独特特性,这些特性可能使它们能够规避一些合成纳米颗粒系统的限制,并促进临床转化。后者特别是与它们固有的稳定性、穿过生物屏障的能力、有效传递生物活性载体或逃避免疫识别有关。此外,我们讨论了 EVs 在诊断和治疗中的潜在作用,并强调了在 EV 能够常规应用于临床实践之前仍需克服的挑战。
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