Skin-permeable gold nanoparticles with modifications azelamide monoethanolamine ameliorate inflammatory skin diseases
He Zhao, Han Zhao, Yan Tang, Mengfan Li, Yisheng Cai, Xinke Xiao, Fanping He, Hongwen Huang, Yiya Zhang, Ji Li
Abstract
BACKGROUND: Traditional topical drug delivery for treating inflammatory skin diseases suffers from poor skin penetration and long-term side effects. Metal nanoparticles show promising application in topical drug delivery for inflammatory skin diseases. METHODS: Here, we synthesized a new type of nanoparticles, azelamide monoethanolamine-functionalized gold nanoparticles (Au-MEA NPs), based on citrate-capped gold nanoparticles (Au-CA NPs) via the ligand exchange method. The physical and chemical properties of Au-CA NPs and Au-MEA NPs were characterized. In vivo studies were performed using imiquimod-induced psoriasis and LL37-induced rosacea animal models, respectively. For in vitro studies, a model of cellular inflammation was established using HaCaT cells stimulated with TNF-α. In addition, proteomics, gelatin zymography, and other techniques were used to investigate the possible therapeutic mechanisms of the Au-MEA NPs. RESULTS: We found that Au-MEA NPs exhibited better stability and permeation properties compared to conventional Au-CA NPs. Transcutaneously administered Au-MEA NPs exerted potent therapeutic efficacy against both rosacea-like and psoriasiform skin dermatitis in vivo without overt signs of toxicity. Mechanistically, Au-MEA NPs reduced the production of pro-inflammatory mediators in keratinocytes by promoting SOD activity and inhibiting the activity of MMP9. CONCLUSION: Au-MEA NPs have the potential to be a topical nanomedicine for the effective and safe treatment of inflammatory skin diseases.