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Effects of Histidine Oligomers in Lipid Nanoparticles on siRNA Delivery
- Title
- Effects of Histidine Oligomers in Lipid Nanoparticles on siRNA Delivery
- Authors
- Lee; Hyeondo; You; Gayeon; Yeo; Sangho; Hyukjin; Mok; Hyejung
- Ewha Authors
- 이혁진
- SCOPUS Author ID
- 이혁진
- Issue Date
- 2024
- Journal Title
- Macromolecular Bioscience
- ISSN
- 1616-5187
- Citation
- Macromolecular Bioscience vol. 24, no. 8
- Keywords
- endosome escape; histidine oligomer; lipid nanoparticle; siRNA delivery
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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. © 2024 Wiley-VCH GmbH.
- DOI
- 10.1002/mabi.202400043
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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