<br>动脉粥样硬化中通过抗CD47抗体偶联的双功能纳米颗粒恢复巨噬细胞功能的细胞内和细胞外协同治疗,Bioactive Materials

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动脉粥样硬化中通过抗CD47抗体偶联的双功能纳米颗粒恢复巨噬细胞功能的细胞内和细胞外协同治疗
Bioactive Materials ( IF 18.0 ) Pub Date : 2024-01-05 , DOI: 10.1016/j.bioactmat.2023.12.024
Qiang Luo ₁ , Liqun Dai ₂ , Junli Li ₁ , Heyanni Chen ₃ , Ying Hao ₁ , Qing Li ₁ , Lili Pan ₄ , Chengxiang Song ₁ , Zhiyong Qian ₂ , Mao Chen ₁

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动脉粥样硬化是全球心血管疾病的重要诱因。有效减少动脉粥样硬化斑块的形成可以减少心血管疾病的发生。因此，控制巨噬细胞的功能至关重要。本研究提出了一种针对巨噬细胞的双功能纳米粒子的创建，以实现细胞内和细胞外协同治疗以恢复巨噬细胞功能。该纳米颗粒与抗CD47抗体缀合，调节巨噬细胞外表面的细胞外CD47-SIRPα吞噬信号轴，并封装NLRP3抑制剂（CY-09）来调节巨噬细胞的细胞内炎症反应。结果表明，纳米粒子在Apoe小鼠的动脉粥样硬化斑块中积聚，改变巨噬细胞的吞噬作用，抑制NLRP3炎症小体的激活，减轻斑块负担，同时确保安全。单细胞 RNA 测序检查表明，这种多功能纳米颗粒可降低与炎症相关的基因表达，并管理斑块病变中的炎症途径。这项研究提出了一种协同治疗方法，利用与抗 CD47 结合的双功能纳米颗粒来调节斑块的微环境。

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Intracellular and extracellular synergistic therapy for restoring macrophage functions via anti-CD47 antibody-conjugated bifunctional nanoparticles in atherosclerosis

Atherosclerosis is a significant contributor to global cardiovascular disease. Reducing the formation of atherosclerotic plaque effectively can lead to a decrease in cardiovascular diseases. Therefore, controlling macrophage function is crucial. This study presents the creation of a bifunctional nanoparticle that is specific to macrophages to achieve intracellular and extracellular synergistic therapy for restoring macrophage functions. The nanoparticle is conjugated with anti-CD47 antibody to modulate extracellular CD47-SIRPα phagocytic signaling axis on the outer surface of macrophages and encapsulates the NLRP3 inhibitor (CY-09) to regulate intracellular inflammation response of macrophages. The results showed that the nanoparticles accumulate in the atherosclerotic plaque, alter macrophage phagocytosis, inhibit NLRP3 inflammasome activation, and decrease the plaque burden in Apoe mice whilst ensuring safety. Examination of single-cell RNA sequencing indicates that this multifunctional nanoparticle decreases the expression of genes linked to inflammation and manages inflammatory pathways in the plaque lesion. This study proposes a synergistic therapeutic approach that utilizes a bifunctional nanoparticle, conjugated with anti-CD47, to regulate the microenvironment of plaques.

更新日期：2024-01-05

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