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调节斑块炎症通过向mRNA纳米颗粒用于治疗动脉样硬化

Mingzhu Gao¹, Maoping Tang¹, William Ho

¹Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of Pharmacy, National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.

|September 5, 2023

概括

这项研究引入了纳米粒子介导的mRNA疗法,以向动脉样硬化的炎症. 该方法成功地将IL-10mRNA传递给巨细胞,减少斑块炎症并改善小鼠模型中的病变稳定性.

科学领域:

生物医学工程生物医学工程
心血管研究研究心血管研究
纳米医学是一种纳米医学.

背景情况:

动脉样硬化涉及慢性炎症,由巨细胞在动脉斑块中的积累驱动.
目前的治疗方法降低了LDL胆固醇,但往往无法预防主要的不良心血管事件.
针对斑块炎症仍然是一个挑战,原因是特异性和有效性问题.

研究的目的:

开发和评估一种纳米粒子 (NP) 介导的mRNA治疗策略,用于向和调节动脉样硬化病变中的炎症.
评估通过NP传递的IL-10mRNA在减少炎症和稳定动脉样硬化斑块方面的有效性.

主要方法:

开发旨在提供编码Interleukin-10 (IL-10) 的mRNA的NP.
针对性NP的静脉注射给西方饮食养的Ldlr-/-小鼠,这些小鼠患有晚期动脉样硬化病变.
评估NP与M2类巨细胞的同位化,IL-10的产生,以及斑块特征的变化.

主要成果:

向的NP成功地与动脉硬化斑块内的M2类巨细胞结合.
在斑块中诱导IL-10的产生,导致显著缓解炎症反应.
已证明减少了氧化应激,巨细胞亡,脂质沉积和死角区域,以及纤维帽厚度增加.

结论:

通过NP介导的mRNA输送IL-10是一种有效的策略,用于针对晚期动脉样硬化中巨驱动的炎症.
这种方法显示出改善动脉样硬化斑块稳定性和降低心血管事件风险的潜力.
针对性NP炎症管理策略对未来的临床转化具有前途.

关键词:

动脉样硬化动脉样硬化解决炎症的IL-10可以消除炎症.损伤性的巨细胞.它们是mRNARNA.有针对性的纳米粒子.

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