期刊
JOURNAL OF CONTROLLED RELEASE
卷 235, 期 -, 页码 195-204出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.06.006
关键词
MicroRNA; Allergy; Non-coding RNA; SiRNA
资金
- EU structural assistance grant [SARMP12219T]
- European Union through the European Regional Development Fund [2014-2020.4.01.15-0012]
- Center of Excellence in Chemical Biology
- Competence Centre on Reproductive Medicine and Biology
- Estonian Ministry of Education and Research [0180019s11, SF0180027s08]
- Estonian Research Council [PUT214, PUT4, PUT177, ETF8932]
- University of Tartu Developmental Fund [MV-1]
- EMBO Installation Grant [1819]
- Estonian Research Council
- Marie Curie Actions
- ERMOS90 fellowship
- Estonian Ministry of Education and Research (EU Regional Development Fund) [10.1-9/12/380 REMARK]
The skin is a difficult to access tissue for efficient delivery of large and/or chargedmacromolecules, including therapeutic DNA and RNA oligonucleotides. Cell-penetrating peptide PepFect6 (PF6) has been shown to be suitable transport vehicle for siRNAs in cell culture and systemically in vivo in mice. MiR-146a is known as anti-inflammatory miRNA that inhibits multiple factors fromthe nuclear factor (NF)-kappa B pathway in various cell types, including keratinocytes. In this study, PF6 was shown to form unimodal nanocomplexes with miR-146a mimic that entered into human primary keratinocytes, where miR-146a inhibited the expression of its direct targets fromthe NF-kappa B pathway and the genes known to be activated by NF-kappa B, C-C motif ligand (CCL)5 and interleukin (IL)-8. The transfection of miR-146a mimic with PF6 was more efficient in sub-confluent keratinocyte cultures, affected keratinocyte proliferation less and had similar effect on cell viability when compared with a lipid based agent. Subcutaneous pre-administration of PF6-miR-146a nanocomplexes attenuated ear-swelling and reduced the expression of pro-inflammatory cytokines and chemokines IL-6, CCL11, CCL24 and C-X-C motif ligand 1 (CXCL1) in a mouse model of irritant contact dermatitis. Our data demonstrates that PF6-miR-146a nanoparticles might have potential in the development of therapeutics to target inflammatory skin diseases. (C) 2016 Elsevier B.V. All rights reserved.
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