Skin-permeable gold nanoparticles with modifications azelamide monoethanolamine ameliorate inflammatory skin diseases.

IF 9.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomarker Research Pub Date : 2024-10-09 DOI:10.1186/s40364-024-00663-0

He Zhao, Han Zhao, Yan Tang, Mengfan Li, Yisheng Cai, Xin Xiao, Fanping He, Hongwen Huang, Yiya Zhang, Ji Li

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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.

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具有改性氮杂环酰胺单乙醇胺的皮肤渗透性金纳米粒子可改善炎症性皮肤病。

背景：传统的局部给药治疗炎症性皮肤病存在皮肤渗透性差和长期副作用的问题。方法：在柠檬酸盐封端的金纳米颗粒（Au-CA NPs）的基础上，通过配体交换法合成了一种新型纳米颗粒--壬二酰胺单乙醇胺功能化金纳米颗粒（Au-MEA NPs）。研究人员对 Au-CA NPs 和 Au-MEA NPs 的物理和化学特性进行了表征。分别使用咪喹莫特诱导的银屑病和 LL37 诱导的酒渣鼻动物模型进行了体内研究。在体外研究中，使用 TNF-α 刺激的 HaCaT 细胞建立了细胞炎症模型。此外，还利用蛋白质组学、明胶酶谱等技术研究了 Au-MEA NPs 可能的治疗机制：我们发现，与传统的 Au-CA NPs 相比，Au-MEA NPs 具有更好的稳定性和渗透性。经皮给药的 Au-MEA NPs 对红斑痤疮样皮肤炎和银屑病样皮肤炎均有显著疗效，且无明显毒性。从机理上讲，Au-MEA NPs 通过促进 SOD 活性和抑制 MMP9 活性，减少了角质形成细胞中促炎介质的产生：结论：Au-MEA NPs 有潜力成为一种局部纳米药物，用于有效、安全地治疗炎症性皮肤病。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomarker Research Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

15.80

自引率

1.80%

发文量

审稿时长

10 weeks

期刊介绍： Biomarker Research, an open-access, peer-reviewed journal, covers all aspects of biomarker investigation. It seeks to publish original discoveries, novel concepts, commentaries, and reviews across various biomedical disciplines. The field of biomarker research has progressed significantly with the rise of personalized medicine and individual health. Biomarkers play a crucial role in drug discovery and development, as well as in disease diagnosis, treatment, prognosis, and prevention, particularly in the genome era.