A novel antimicrobial peptide-derived vehicle for oligodeoxynucleotide delivery to inhibit TNF-α expression

Wei Wen Hu, Shih Chun Huang, Shiow Lian Catherine Jin

研究成果: 雜誌貢獻期刊論文同行評審

3 引文 斯高帕斯(Scopus)

摘要

Indolicidin (IL), an antimicrobial peptide, was investigated as a vehicle to promote oligodeoxynucleotides (ODNs) delivery. To increase charge density, IL was dimerized by adding a cysteine to its C or N terminus, which was denoted as ILC or CIL, respectively. In contrast to IL, cytotoxicity of ILC and CIL was significantly reduced because these dimeric peptides were longer than IL, which restricted their insertions to cell membrane. In contrast to ILC, CIL displayed well loading efficiency. These peptides were applied to deliver ODNs against tumor necrosis factor-α (TNF-α) because TNF-α is a pro-inflammatory cytokine which plays an important role in immunological diseases. Although IL/ODN slightly reduced TNF-α expression, the high cytotoxicity restricted its application window. Furthermore, ILC/ODN was incapable of inducing gene silence due to its low encapsulation efficiency and poor endosomal escape. In contrast, CIL exhibited excellent ODN transportation and the internalized CIL/ODN complexes may escape from endosomes. Therefore, TNF-α expression can be specifically reduced by CIL/ODN complexes, and the silence effect was maintained longer than 14 h. This study provides a useful strategy of peptide vehicle design, which may facilitate the delivery of not only ODN but also other oligonucleotides, including siRNA and miRNA, to promote gene silence application.

原文???core.languages.en_GB???
頁(從 - 到)63-71
頁數9
期刊International Journal of Pharmaceutics
558
DOIs
出版狀態已出版 - 10 3月 2019

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