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Switch off inflammation in spleen cells with CD40-targeted PLGA nanoparticles containing dimethyl fumarate
Colloids and Surfaces B: Biointerfaces ( IF 5.8 ) Pub Date : 2021-09-01 , DOI: 10.1016/j.colsurfb.2021.112091
Sahar Khosravi 1 , Hassan Bardania 2 , Reza Mansouri 1 , Mohammad Taher Tahoori 1 , Fereshte Ghafari 1 , Adel Mohammadzadeh 3 , Mohamad Hassan Fouani 4 , Ali Akbar Pourfathollah 5 , Masoud Soleimani 6
Affiliation  

The purpose of this study was designing and synthesizing a PLGA formulation targeted with anti-CD40 monoclonal antibody, which has suitable physicochemical properties as a dimethyl fumarate (DMF) drug delivery system having minimal cytotoxicity. Therefore, this research was performed to determine the effect of anti-CD40mAb-DMF-NPs on the expression of IL-1β, IL-6 and TNF-α cytokine genes in mouse splenocytes. The toxicity of different groups, namely free PLGA, free DMF, DMF-containing PLGA, anti-CD40mAb-DMF-NPs, was evaluated by MTT assay. PLGA formulations conjugated with mAbCD40 were loaded with DMF drug that showed little cytotoxic effect against mouse splenocytes. QRT-PCR method was subsequently used to assess the effect of the mentioned groups on the expression of IL-1β, TNF-α and IL-6 genes. After treatment of the cells with DMF alone or with polymer carriers, the expression of IL-1β, IL-6 and TNF-α cytokine genes was significantly reduced. The decrease in expression was markedly higher in the antibody-targeted nanoparticles group relative to other treatment groups. Our results in this area are promising and provide a good basis for further future studies in this regard.



中文翻译:

使用含有富马酸二甲酯的 CD40 靶向 PLGA 纳米颗粒关闭脾细胞的炎症

本研究的目的是设计和合成以抗 CD40 单克隆抗体为靶向的 PLGA 制剂,该制剂具有合适的理化特性,可作为富马酸二甲酯 (DMF) 药物递送系统,具有最小的细胞毒性。因此,本研究旨在确定抗 CD40mAb-DMF-NPs 对小鼠脾细胞中 IL-1β、IL-6 和 TNF-α 细胞因子基因表达的影响。通过MTT法评估不同组的毒性,即游离PLGA、游离DMF、含DMF的PLGA、抗CD40mAb-DMF-NPs。与 mAbCD40 偶联的 PLGA 制剂装载有对小鼠脾细胞几乎没有细胞毒性作用的 DMF 药物。随后使用QRT-PCR方法评估上述组对IL-1β、TNF-α和IL-6基因表达的影响。单独用DMF或聚合物载体处理细胞后,IL-1β、IL-6和TNF-α细胞因子基因的表达显着降低。与其他治疗组相比,抗体靶向纳米颗粒组的表达降低显着更高。我们在这方面的结果很有希望,并为未来在这方面的进一步研究提供了良好的基础。

更新日期:2021-09-08
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