气溶胶吸入靶向炎症细胞的树枝状聚合物-地塞米松共轭物,用于过敏性哮喘的高效治疗。

IF 1.6 4区 医学 Q4 BIOPHYSICS
Biointerphases Pub Date : 2024-03-01 DOI:10.1116/6.0003480
Danfei Chen, Xiaobo Xuan, Yuyan Chen, Xia Fang, Liwei Liu, Guowei Wang, Jian Chen
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引用次数: 0

摘要

过敏性哮喘(AA)是一种常见的呼吸系统疾病,临床特点是急性和持续性炎症的高发率。然而,目前治疗 AA 的方法缺乏有效性和多样性。在这项研究中,我们发现γ-谷氨酰转移酶(GGT)的细胞膜受体在 AA 病例中浸润肺组织的炎症细胞上高度过表达。因此,我们开发了一种GGT特异性树枝状聚合物-地塞米松共轭物(GSHDDC),可通过气溶胶吸入来快速、持续地治疗AA。通过碳酸酯连接和氨基迈克尔加成,6-羟基己基丙烯酸酯修饰的地塞米松与聚酰胺胺树枝状聚合物共价连接,然后用谷胱甘肽的GGT底物对树枝状聚合物进行表面修饰,就制成了GSHDDC。AA 小鼠吸入气溶胶后,小颗粒大小的 GSHDDC 很容易扩散到肺泡,并通过谷胱甘肽配体/GGT 受体介导的识别与炎症细胞接触。炎症细胞表面过量表达的 GGT 会引发谷胱甘肽的γ-谷氨酰转移反应,生成带正电荷的伯胺,从而诱导阳离子化介导的细胞内吞迅速进入炎症细胞。地塞米松通过细胞内酶水解逐渐释放,从而在卵清蛋白诱导的 AA 小鼠体内产生持续的抗炎效果(如减少嗜酸性粒细胞浸润、降低炎症因子水平)。这项研究表明,吸入性和活性炎症细胞靶向树枝状聚合物-地塞米松共轭物可有效治疗 AA。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Aerosol inhalation of inflammatory cells-targeted dendrimer-dexamethasone conjugate for efficient allergic asthma therapy.

Allergic asthma (AA) is a common breathing disorder clinically characterized by the high occurrence of acute and continuous inflammation. However, the current treatment options for AA are lacking in effectiveness and diversity. In this study, we determined that the cell membrane receptor of gamma-glutamyl transferase (GGT) was highly overexpressed on the inflammatory cells that infiltrate the pulmonary tissues in AA cases. Therefore, we developed a GGT-specific dendrimer-dexamethasone conjugate (GSHDDC) that could be administered via aerosol inhalation to treat AA in a rapid and sustained manner. The GSHDDC was fabricated by the covalent attachment of 6-hydroxyhexyl acrylate-modified dexamethasone to polyamidoamine dendrimers via a carbonic ester linkage and the amino Michael addition, followed by the surface modification of the dendrimers with the GGT substrate of glutathione. After aerosol inhalation by the AA mice, the small particle-sized GSHDDC could easily diffuse into pulmonary alveoli and touch with the inflammatory cells via the glutathione ligand/GGT receptor-mediated recognition. The overexpressed GGT on the surface of inflammatory cells then triggers the gamma-glutamyl transfer reactions of glutathione to generate positively charged primary amines, thereby inducing rapid cationization-mediated cellular endocytosis into the inflammatory cells. The dexamethasone was gradually released by the intracellular enzyme hydrolysis, enabling sustained anti-inflammatory effects (e.g., reducing eosinophil infiltration, decreasing the levels of inflammatory factors) in the ovalbumin-induced AA mice. This study demonstrates the effectiveness of an inhalational and active inflammatory cells-targeted dendrimer-dexamethasone conjugate for efficient AA therapy.

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来源期刊
Biointerphases
Biointerphases 生物-材料科学:生物材料
自引率
0.00%
发文量
35
期刊介绍: Biointerphases emphasizes quantitative characterization of biomaterials and biological interfaces. As an interdisciplinary journal, a strong foundation of chemistry, physics, biology, engineering, theory, and/or modelling is incorporated into originated articles, reviews, and opinionated essays. In addition to regular submissions, the journal regularly features In Focus sections, targeted on specific topics and edited by experts in the field. Biointerphases is an international journal with excellence in scientific peer-review. Biointerphases is indexed in PubMed and the Science Citation Index (Clarivate Analytics). Accepted papers appear online immediately after proof processing and are uploaded to key citation sources daily. The journal is based on a mixed subscription and open-access model: Typically, authors can publish without any page charges but if the authors wish to publish open access, they can do so for a modest fee. Topics include: bio-surface modification nano-bio interface protein-surface interactions cell-surface interactions in vivo and in vitro systems biofilms / biofouling biosensors / biodiagnostics bio on a chip coatings interface spectroscopy biotribology / biorheology molecular recognition ambient diagnostic methods interface modelling adhesion phenomena.
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