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载有抗 TNF-α 抗体和硫酸软骨素的 PAMAM 树枝状聚合物,用于治疗类风湿性关节炎。

PAMAM dendrimers functionalised with an anti-TNF α antibody and chondroitin sulphate for treatment of rheumatoid arthritis.

机构信息

Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães 4805-017, Portugal.

Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães 4805-017, Portugal; The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at University of Minho, Avepark, 4805-017 Barco, Guimarães, Portugal.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Feb;121:111845. doi: 10.1016/j.msec.2020.111845. Epub 2021 Jan 6.

Abstract

Rheumatoid arthritis is a chronic autoimmune disease characterised by joint synovial inflammation, along with cartilage and bone tissue destruction. Dendrimers can offer new opportunities as drug delivery systems of molecules of interest. Herein we aimed to develop poly(amidoamine) dendrimers (PAMAM), functionalised with chondroitin sulphate (CS), lined with anti-TNF α antibodies (Abs) to provide anti-inflammatory properties. Physicochemical characterisation demonstrated that anti-TNFα Abs-CS/PAMAM dendrimer NPs were successfully produced. The in vitro studies revealed that CS/PAMAM dendrimer NPs did not affect the ATDC5 and THP-1 cell lines' metabolic activity and proliferation, presenting good cytocompatibility and hemocompatibility. Moreover, anti-TNFα Abs-CS/PAMAM dendrimer NPs showed suitable TNF α capture capacity, making them appealing for new immunotherapies in RA patients.

摘要

类风湿关节炎是一种慢性自身免疫性疾病,其特征是关节滑膜炎症,同时伴有软骨和骨组织破坏。树状聚合物可以为具有治疗作用的分子提供新的药物传递系统的机会。在此,我们旨在开发聚(酰胺-胺)树突状聚合物(PAMAM),用硫酸软骨素(CS)进行功能化,并用抗 TNFα 抗体(Abs)进行修饰,以提供抗炎特性。物理化学特性表明成功制备了抗 TNFα Abs-CS/PAMAM 树突状聚合物 NPs。体外研究表明 CS/PAMAM 树突状聚合物 NPs 不会影响 ATDC5 和 THP-1 细胞系的代谢活性和增殖,表现出良好的细胞相容性和血液相容性。此外,抗 TNFα Abs-CS/PAMAM 树突状聚合物 NPs 具有合适的 TNFα 捕获能力,这使得它们成为 RA 患者新的免疫疗法的有吸引力的选择。

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