脂质纳米颗粒中的组氨酸低聚物对 siRNA 递送的影响

IF 4.4 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hyeondo Lee, Gayeon You, Sangho Yeo, Hyukjin Lee, Hyejung Mok
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引用次数: 0

摘要

本研究开发了组氨酸寡聚体(oHis;10mer)结合型 LNPs(H10LNPs),作为高效递送 siRNA 的新型载体。值得注意的是,未修饰的组氨酸寡聚体(oHis;10mer)通过与 siRNA 的离子相互作用被大量整合到 LNPs 中,从而成为一种内质体逃逸增强剂。H10LNPs 大小约为 65 nm,通过钙黄绿素检测和共聚焦显微镜下的细胞内荧光图像证明,H10LNPs 的内体逃逸程度明显提高,超过了传统的 LNPs。此外,与 LNP 处理的细胞相比,H10LNPs 处理的细胞中人内源性球糖基甘油酰胺合成酶(Gb3 合成酶)基因的半数抑制浓度(IC50)显著降低了三倍。值得注意的是,H10LNPs 在体外和体内都保持了相当的生物相容性和生物分布。考虑到所制备的 siRNA H10LNPs 具有良好的生物相容性和优于传统 LNPs 的基因沉默活性,这些颗粒可用于安全递送治疗用 siRNA。此外,本研究还介绍了将未修饰的功能性阳离子肽整合到 LNPs 中的前景广阔、可行、简单的替代配方工艺,以提高多种核酸类药物的递送效率。本文受版权保护。保留所有权利。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Effects of Histidine Oligomers in Lipid Nanoparticles on siRNA Delivery

Effects of Histidine Oligomers in Lipid Nanoparticles on siRNA Delivery

In this study, histidine oligomer (oHis; 10mer)-incorporating LNPs (H10LNPs) are developed as a novel carrier for efficient siRNA delivery. Notably, the unmodified oHis (10mer) is greatly incorporated within LNPs through ionic interaction with siRNAs, which serves as an endosome escape enhancer. H10LNPs with a size of ≈65 nm demonstrate a significantly enhanced extent of endosomal escape, as evidenced by calcein assay and confocal microscopy images of intracellular fluorescence, surpassing conventional LNPs. Furthermore, the half inhibitory concentration (IC50) of the human endogenous globotriaosylceramide synthase (Gb3 synthase) gene in H10LNPs-treated cells exhibits a significant threefold decrease, compared to that in LNP-treated cells. Notably, H10LNPs maintain comparable biocompatibility and biodistribution both in vitro and in vivo. Considering that the fabricated siRNA H10LNPs exhibit excellent biocompatibility and superior gene silencing activity over conventional LNPs, these particles can be harnessed for the safe delivery of therapeutic siRNAs. Additionally, this study introduces promising, feasible, simple, and alternative formulation processes for integrating unmodified functional cationic peptides into LNPs to enhance the delivery efficiency of a wide range of nucleic acid-based drugs.

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来源期刊
Macromolecular bioscience
Macromolecular bioscience 生物-材料科学:生物材料
CiteScore
7.90
自引率
2.20%
发文量
211
审稿时长
1.5 months
期刊介绍: Macromolecular Bioscience is a leading journal at the intersection of polymer and materials sciences with life science and medicine. With an Impact Factor of 2.895 (2018 Journal Impact Factor, Journal Citation Reports (Clarivate Analytics, 2019)), it is currently ranked among the top biomaterials and polymer journals. Macromolecular Bioscience offers an attractive mixture of high-quality Reviews, Feature Articles, Communications, and Full Papers. With average reviewing times below 30 days, publication times of 2.5 months and listing in all major indices, including Medline, Macromolecular Bioscience is the journal of choice for your best contributions at the intersection of polymer and life sciences.
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