Lasse Hagedorn, David C. Jürgens, Olivia M. Merkel, Benjamin Winkeljann
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引用次数: 0
摘要
生物制剂和基于 RNA 的疗法的兴起挑战了传统药物治疗的局限性。然而,这些强效的新型疗法需要有效的递送系统才能充分发挥其潜力。脂质纳米颗粒(LNPs)已成为一种很有前景的 RNA 递送解决方案,但其内贮器禁锢仍是一个关键障碍。相比之下,天然细胞外囊泡(EVs)具有克服内体降解的内在机制,与传统的 LNPs 相比,EVs 表现出更优越的内体逃逸(EE)能力。这篇微型综述探讨了基于脂质纳米粒子的药物递送所面临的EE挑战,并深入探讨了EV的逃逸机制,从而推动了用于RNA治疗的LNP设计。我们将 EV 的天然 EE 策略与 LNP 中使用的 EE 策略进行了比较,并重点介绍了当代的 LNP 设计方法。通过了解 EE 的机制,我们将能开发出更有效的药物递送载体,提高基于 RNA 的疗法的递送和疗效。
Endosomal escape mechanisms of extracellular vesicle-based drug carriers: lessons for lipid nanoparticle design
The rise of biologics and RNA-based therapies challenges the limitations of traditional drug treatments. However, these potent new classes of therapeutics require effective delivery systems to reach their full potential. Lipid nanoparticles (LNPs) have emerged as a promising solution for RNA delivery, but endosomal entrapment remains a critical barrier. In contrast, natural extracellular vesicles (EVs) possess innate mechanisms to overcome endosomal degradation, demonstrating superior endosomal escape (EE) compared to conventional LNPs. This mini review explores the challenges of EE for lipid nanoparticle-based drug delivery, and offers insights into EV escape mechanisms to advance LNP design for RNA therapeutics. We compare the natural EE strategies of EVs with those used in LNPs and highlight contemporary LNP design approaches. By understanding the mechanisms of EE, we will be able to develop more effective drug delivery vehicles, enhancing the delivery and efficacy of RNA-based therapies.