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

Abstract:

: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.

journal_name

Int J Pharm

authors

Hu WW,Huang SC,Jin SC

doi

10.1016/j.ijpharm.2018.12.082

subject

Has Abstract

pub_date

2019-03-10 00:00:00

pages

63-71

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(19)30019-5

journal_volume

558

pub_type

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