Systemic delivery of small interfering RNA targeting nuclear factor κB in mice with collagen-induced arthritis using arginine-histidine-cysteine based oligopeptide-modified polymer nanomicelles

被引：36

作者：

Kanazawa, Takanori ^{[1
]}

Endo, Takahiro ^{[1
]}

Arima, Naoki ^{[1
]}

Ibaraki, Hisako ^{[1
]}

Takashima, Yuuki ^{[1
]}

Seta, Yasuo ^{[1
]}

机构：

[1] Tokyo Univ Pharm & Life Sci, Sch Pharm, 1432-1 Horinouchi, Hachioji, Tokyo 1920392, Japan

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2016年 / 515卷 / 1-2期

关键词：

Rheumatoid arthritis; Polymeric micelles; Systemic siRNA delivery; Nuclear factor kappa B; RelA; Functional peptides; CELL-PENETRATING PEPTIDE; RHEUMATOID-ARTHRITIS; FUNCTIONAL PEPTIDES; SIRNA; NANOCARRIERS; AGENTS;

D O I：

10.1016/j.ijpharm.2016.10.033

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

This study aimed to build an innovative system to deliver a systemic small interfering RNA (siRNA) treatment for rheumatoid arthritis. We combined arginine-histidine-cysteine based oligopeptide-modified polymer micelles with siRNA targeting the nuclear factor kappa B subunit, RelA (siRelA). This is a key molecule in the control of inflammation. We tested the cellular uptake of siRNA and its effects on inflammatory cytokine levels in vitro using synoviocytes, and siRNA distribution and therapeutic effects in vivo in mice with collagen-induced arthritis (CIA). These studies showed that arginine-histidine based oligopeptide modified micelles produced effective cellular siRNA uptake and suppressed inflammatory cytokine levels in synoviocytes. In vivo, these micelles produced marked accumulation of siRNAs in arthritic paws in CIA mice, with much less accumulation in healthy mice. The siRelA-polymer micelle complexes also produced more effective suppression of RelA mRNA expression and inflammatory cytokine levels in the arthritic paws of CIA mice and reduced their clinical symptom scores and paw thickness. (C) 2016 Elsevier B.V. All rights reserved.

引用

页码：315 / 323

页数：9

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