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针对针对性动脉样硬化治疗的多途径调节使用抗miR-33载荷DNA原始化
Yuxuan Ma1,2, Qi Wang1,2, Shiyu Du1,2
1Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu 210023, P. R. China.
ACS nano
|February 7, 2024
概括
一种新的DNA纳米结构,cRGD/ASO tDON,通过减少炎症和泡细胞形成,为动脉样硬化提供了向组合疗法. 这种方法显示出管理这种慢性炎症疾病的巨大潜力.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 心血管研究研究心血管研究
背景情况:
- 动脉样硬化 (AS) 是一种慢性炎症性疾病,具有复杂的,多因素的致病性.
- 组合疗法是解决AS复杂机制的一个有希望的策略.
- 有针对性的输送系统可以提高治疗效果,并最大限度地减少副作用.
研究的目的:
- 开发和评估一种新的DNA原始结构纳米结构,cRGD/ASO tDON,用于动脉样硬化向组合治疗.
- 研究cRGD/ASO tDON在调节AS中的炎症反应和脂质代谢中的作用机制.
- 在临床前模型中评估cRGD/ASO tDON的抗动脉样硬化疗效和安全性.
主要方法:
- 自组装DNA原木纳米结构 (cRGD/ASO tDON) 的制造.
- 向在动脉样硬化病变中的巨细胞和内皮细胞上过度表达的αvβ3整合素受体.
- 对氧化应激,巨细胞极化和泡细胞形成 (miR-33下调) 的影响的评估.
- 在动脉样硬化小鼠模型中的体内验证,将疗效与probucol进行比较.
主要成果:
- cRGD/ASO tDON有效地针对动脉样硬化病变.
- 纳米结构减轻了氧化应激,促进了M2巨细胞的两极分化,并抑制了泡细胞的形成.
- 在体内研究表明,AS进展的逆转和动脉平衡的恢复.
- 与probucol相比,cRGD/ASO tDON在较低的剂量下取得了治疗结果.
结论:
- 使用自组装DNA纳米配方的向组合疗法是治疗动脉样硬化的可行策略.
- cRGD/ASO tDON显示出显著的抗动脉样硬化疗效和有利的安全性.
- 这项研究强调了DNA纳米结构在解决多因子炎症疾病方面的潜力.
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