期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 124, 期 10, 页码 4363-4374出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI75673
关键词
-
资金
- NIH grants [AI049261, AR056468]
- Department of Medicine at Washington University
- Sigma-Aldrich Predoctoral Fellowship
- NIH [HL073646, HL112303, DK095555, AR056223]
- James R. Hornsby Family Dream Garden Investment Partnership
- NIH grant [P30 AR057235]
The NF-kappa B signaling pathway is implicated in various inflammatory diseases, including rheumatoid arthritis (RA); therefore, inhibition of this pathway has the potential to ameliorate an array of inflammatory diseases. Given that NF-kappa B signaling is critical for many immune cell functions, systemic blockade of this pathway may lead to detrimental side effects. siRNAs coupled with a safe and effective delivery nanoplatform may afford the specificity lacking in systemic administration of small-molecule inhibitors. Here we demonstrated that a melittin-derived cationic amphipathic peptide combined with siRNA targeting the p65 subunit of NF-kappa B (p5RHH-p65) noncovalently self-assemble into stable nanocomplexes that home to the inflamed joints in a murine model of RA. Specifically, administration of p5RHH-p65 siRNA nanocomplexes abrogated inflammatory cytokine expression and cellular influx into the joints, protected against bone erosions, and preserved cartilage integrity. The p5RHH-p65 siRNA nanocomplexes potently suppressed early inflammatory arthritis without affecting p65 expression in off-target organs or eliciting a humoral response after serial injections. These data suggest that this self-assembling, largely nontoxic platform may have broad utility for the specific delivery of siRNA to target and limit inflammatory processes for the treatment of a variety of diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据