Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis.,Nature Nanotechnology

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Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis.
Nature Nanotechnology ( IF 38.1 ) Pub Date : 2020-01-27 , DOI: 10.1038/s41565-019-0619-3
Alyssa M Flores ₁ , Niloufar Hosseini-Nassab ₂ , Kai-Uwe Jarr ₁ , Jianqin Ye ₁ , Xingjun Zhu ₂ , Robert Wirka ₃ , Ai Leen Koh ₄ , Pavlos Tsantilas ₁ , Ying Wang ₁ , Vivek Nanda ₁ , Yoko Kojima ₁ , Yitian Zeng ₄ , Mozhgan Lotfi ₁ , Robert Sinclair ₄ , Irving L Weissman ₅ , Erik Ingelsson _{3,

6} , Bryan Ronain Smith _{2,

7,

8} , Nicholas J Leeper _{1,

3,

6}

Affiliation

Atherosclerosis is the process that underlies heart attack and stroke. A characteristic feature of the atherosclerotic plaque is the accumulation of apoptotic cells in the necrotic core. Prophagocytic antibody-based therapies are currently being explored to stimulate the phagocytic clearance of apoptotic cells; however, these therapies can cause off-target clearance of healthy tissues, which leads to toxicities such as anaemia. Here we developed a macrophage-specific nanotherapy based on single-walled carbon nanotubes loaded with a chemical inhibitor of the antiphagocytic CD47-SIRPα signalling axis. We demonstrate that these single-walled carbon nanotubes accumulate within the atherosclerotic plaque, reactivate lesional phagocytosis and reduce the plaque burden in atheroprone apolipoprotein-E-deficient mice without compromising safety, and thereby overcome a key translational barrier for this class of drugs. Single-cell RNA sequencing analysis reveals that prophagocytic single-walled carbon nanotubes decrease the expression of inflammatory genes linked to cytokine and chemokine pathways in lesional macrophages, which demonstrates the potential of 'Trojan horse' nanoparticles to prevent atherosclerotic cardiovascular disease.

中文翻译：

前细胞纳米粒子被病变巨噬细胞特异性吸收并预防动脉粥样硬化。

动脉粥样硬化是心脏病发作和中风的基础过程。动脉粥样硬化斑块的一个特征是坏死核心中凋亡细胞的积累。目前正在探索基于吞噬细胞抗体的疗法，以刺激凋亡细胞的吞噬清除；然而，这些疗法可能会导致健康组织的脱靶清除，从而导致贫血等毒性。在这里，我们开发了一种基于单壁碳纳米管的巨噬细胞特异性纳米疗法，该碳纳米管负载有抗吞噬细胞 CD47-SIRPα 信号轴的化学抑制剂。我们证明这些单壁碳纳米管在动脉粥样硬化斑块内积聚，重新激活病变吞噬作用并减少动脉粥样硬化易发性载脂蛋白E缺陷小鼠的斑块负担，而不会影响安全性，从而克服了此类药物的关键转化障碍。单细胞RNA测序分析表明，前噬细胞单壁碳纳米管降低了病变巨噬细胞中与细胞因子和趋化因子途径相关的炎症基因的表达，这证明了“特洛伊木马”纳米颗粒预防动脉粥样硬化性心血管疾病的潜力。

更新日期：2020-01-27

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