A ROS and shear stress dual-sensitive bionic system with cross-linked dendrimers for atherosclerosis therapy,Nanoscale

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A ROS and shear stress dual-sensitive bionic system with cross-linked dendrimers for atherosclerosis therapy
Nanoscale ( IF 5.8 ) Pub Date : 2021-11-17 , DOI: 10.1039/d1nr05355h
Meili Shen _{1,

2} , Shunyu Yao _{1,

2} , Shaojing Li _{1,

2} , Xiaodong Wu _{1,

2} , Shun Liu _{1,

2} , Qingbiao Yang _{1,

2} , Jianshi Du ₃ , Jingyuan Wang _{1,

2} , Xiangyu Zheng ₄ , Yapeng Li _{1,

2}

Affiliation

Atherosclerosis is an important pathological basis for cardiovascular disease. Thus, the treatment of atherosclerosis can effectively improve the prognosis and reduce the mortality of cardiovascular diseases. In this study, we developed simvastatin acid (SA)-loaded cross-linked dendrimer nanoparticles (SA PAM) that were adsorbed to the surface of red blood cells (RBCs) to obtain SA PAM@RBCs, a ROS and shear stress dual response drug delivery system for the treatment of atherosclerosis. SA PAM could continuously release SA in an H₂O₂-triggered manner, and effectively eliminate excessive H₂O₂ in LPS-stimulated RAW 264.7 cells, achieving the target of using the special microenvironment at the plaque to release drugs. At the same time, the shear sensitive model also proved that only 12.4% of SA PAM detached from the RBCs under low shear stress (20 dynes per cm²), while 61.3% SA PAM desorbed from the RBCs under a high shear stress (100 dynes per cm²) stimulus, revealing that SA PAM could desorb in response to the shear stress stimulus. Both the FeCl₃ model and ApoE^−/− model showed that SA PAM@RBCs had better therapeutic effects than free SA, and with excellent safety in vivo. Therefore, a biomimetic drug delivery system with dual sensitivity to ROS and shear stress would become a promising strategy for the treatment of atherosclerosis.

中文翻译：

用于动脉粥样硬化治疗的具有交联树枝状聚合物的 ROS 和剪切应力双敏感仿生系统

动脉粥样硬化是心血管疾病的重要病理基础。因此，动脉粥样硬化的治疗可以有效改善心血管疾病的预后，降低死亡率。在这项研究中，我们开发了负载辛伐他汀酸 (SA) 的交联树枝状大分子纳米粒子 (SA PAM)，将其吸附到红细胞 (RBC) 表面以获得 SA PAM@RBCs，一种 ROS 和剪切应力双重反应药物用于治疗动脉粥样硬化的输送系统。SA PAM能够以H ₂ O ₂触发的方式持续释放SA ，有效去除过量的H ₂ O ₂在LPS刺激的RAW 264.7细胞中，达到利用斑块处特殊微环境释放药物的目的。同时，剪切敏感模型还证明，在低剪切应力（20 dynes/cm ²）下，只有 12.4% 的 SA PAM 从红细胞上脱离，而在高剪切应力（100达因每厘米² ) 刺激，表明 SA PAM 可以响应剪切应力刺激而解吸。FeCl ₃模型和ApoE ^-/-模型均表明SA PAM@RBCs比游离SA具有更好的治疗效果，并且在体内具有出色的安全性. 因此，对ROS和剪切应力具有双重敏感性的仿生药物递送系统将成为治疗动脉粥样硬化的有前途的策略。

更新日期：2021-11-29

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