Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.
Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA; Department of Medicine, Division of Nephrology and Hypertension, University of Southern California, Los Angeles, CA, USA; Department of Surgery, Division of Vascular Surgery and Endovascular Therapy, University of Southern California, Los Angeles, CA, USA.
Mol Aspects Med. 2022 Feb;83:100991. doi: 10.1016/j.mam.2021.100991. Epub 2021 Aug 5.
The use of a variety of RNA molecules, including messenger RNA, small interfering RNA, and microRNA, has shown great potential for prevention and therapy of many pathologies. However, this therapeutic promise has historically been limited by short in vivo half-life, lack of targeted delivery, and safety issues. Nanoparticle (NP)-mediated delivery has been a successful platform to overcome these limitations, with multiple formulations already in clinical trials and approved by the FDA. Although there is a diversity of NPs in terms of material formulation, size, shape, and charge that have been proposed for biomedical applications, specific modifications are required to facilitate sufficient RNA delivery and adequate therapeutic effect. This includes optimization of (i) RNA incorporation into NPs, (ii) specific cell targeting, (iii) cellular uptake and (iv) endosomal escape ability. In this review, we summarize the methods by which NPs can be modified for RNA delivery to achieve optimal therapeutic effects.
多种 RNA 分子（包括信使 RNA、小干扰 RNA 和 microRNA）的应用在许多病理的预防和治疗方面显示出巨大的潜力。然而，这种治疗前景在历史上受到体内半衰期短、靶向递送缺乏和安全性问题的限制。纳米颗粒（NP）介导的递药已成为克服这些限制的成功平台，已有多种制剂正在临床试验中，并获得 FDA 的批准。尽管在材料配方、大小、形状和电荷方面有多种 NPs 被提出用于生物医学应用，但需要进行特定的修饰以促进足够的 RNA 递药和足够的治疗效果。这包括优化 (i) RNA 整合到 NPs 中，(ii) 特定细胞靶向，(iii) 细胞摄取和 (iv) 内涵体逃逸能力。在这篇综述中，我们总结了 NPs 可以修饰的方法，以实现 RNA 递药的最佳治疗效果。
