Hagedorn Lasse, Jürgens David C, Merkel Olivia M, Winkeljann Benjamin
Department of Pharmacy, Ludwig-Maximilians-Universität München, München 81377, Germany.
Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München, München 80799, Germany.
Extracell Vesicles Circ Nucl Acids. 2024 Jul 5;5(3):344-357. doi: 10.20517/evcna.2024.19. eCollection 2024.
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.
生物制剂和基于RNA的疗法的兴起对传统药物治疗的局限性提出了挑战。然而，这些强大的新型治疗药物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RNA递送的一种有前景的解决方案，但内体截留仍然是一个关键障碍。相比之下，天然细胞外囊泡（EVs）具有克服内体降解的固有机制，与传统的LNPs相比，显示出卓越的内体逃逸（EE）能力。这篇小型综述探讨了基于脂质纳米颗粒的药物递送中内体逃逸的挑战，并深入了解了EVs的逃逸机制，以推动用于RNA治疗的LNP设计。我们将EVs的天然EE策略与LNPs中使用的策略进行比较，并突出当代LNP设计方法。通过了解EE的机制，我们将能够开发出更有效的药物递送载体，提高基于RNA的疗法的递送效率和疗效。
