布地奈德联合可吸入脂质纳米颗粒用于抗tslp纳米体mRNA递送治疗类固醇抵抗性哮喘。

IF 15.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Jia Huang, Xin Bai, William Stewart, Xiaoyang Xu, Xue-Qing Zhang
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引用次数: 0

摘要

由于气道上皮的破坏,哮喘加重和类固醇抵抗发生,限制了皮质类固醇的有效性。尽管单克隆抗体已逐渐成为类固醇抵抗性哮喘的辅助治疗,但临床仍需要疗效更好、脱靶效应更小的靶向抗炎治疗。在这里,我们提出了ASCEND(替代类固醇与mRNA编码纳米体共同递送)方法,该方法利用布地奈德(iLNPBUD5)配制的可吸入脂质纳米颗粒递送编码胸腺基质淋巴生成素纳米体(mnbTSLP)的mRNA,用于治疗类固醇抵抗性哮喘。雾化后,mnbTSLP-iLNPBUD5靶向肺部,在递送布地奈德的同时增强抗tslp纳米体的产生。这种联合治疗可以减少小鼠模型中的气道炎症、重塑和高反应性。此外,mnbTSLP通过抑制关键炎症通路恢复类固醇抵抗性哮喘小鼠对布地奈德的敏感性。与皮质类固醇或抗tslp抗体治疗相比,ASCEND方法显示出优越的效果,为类固醇抵抗性哮喘和潜在的其他呼吸系统疾病提供了有前途的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Budesonide-incorporated inhalable lipid nanoparticles for antiTSLP nanobody mRNA delivery to treat steroid-resistant asthma.

Asthma exacerbations and steroid resistance occur due to disruption of the airway epithelium, limiting the effectiveness of corticosteroids. Although monoclonal antibodies have progressively emerged as adjunctive therapy for steroid-resistant asthma, there remains a clinical need for targeted anti-inflammatory therapies with better efficacy and fewer off-target effects. Here, we propose the ASCEND (Alternative Steroids Co-delivering with mRNA Encoding Nanobodies) approach, which utilizes inhalable lipid nanoparticles formulated with budesonide (iLNPBUD5) to deliver mRNA encoding a thymic stromal lymphopoietin nanobody (mnbTSLP) for the treatment of steroid-resistant asthma. Upon nebulization, mnbTSLP-iLNPBUD5 targets the lungs, enhancing antiTSLP nanobody production while delivering budesonide. This combined therapy reduces airway inflammation, remodeling, and hyperresponsiveness in murine models. Additionally, mnbTSLP restores the sensitivity of steroid-resistant asthmatic mice to budesonide by inhibiting key inflammatory pathways. The ASCEND approach shows superior effects compared to corticosteroid or antiTSLP antibody treatments, offering a promising strategy for steroid-resistant asthma and potentially other respiratory diseases.

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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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