Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
J Control Release. 2021 Jan 10;329:445-453. doi: 10.1016/j.jconrel.2020.11.064. Epub 2020 Dec 4.
Atherosclerosis is a kind of chronic inflammatory diseases characterized by dysfunction of local immune responses. Here we engineer platelet-derived extracellular vesicles (PEVs) to load MCC950, an NLRP3-inflammasome inhibitor, for atherosclerosis-targeted therapy. PEVs which are readily collected from the activated platelets selectively bind multiple cell types associated with the formation of atherosclerotic plaque in vivo. Intravenous administration of MCC950-PEVs could significantly reduce the formation of atherosclerotic plaques, lower the local inflammation and inhibit proliferation of macrophages and T cells at the plaque site compared with free drug administration in ApoE-KO mice. Our strategy suggests the promise of PEVs for targeted drug delivery for treatment of atherosclerosis.
动脉粥样硬化是一种以局部免疫反应功能障碍为特征的慢性炎症性疾病。在这里，我们设计了血小板衍生的细胞外囊泡（PEVs）来装载 NLRP3 炎性小体抑制剂 MCC950，用于动脉粥样硬化的靶向治疗。PEVs 很容易从激活的血小板中收集，在体内选择性地结合与动脉粥样硬化斑块形成有关的多种细胞类型。与在 ApoE-KO 小鼠中给予游离药物相比，静脉给予 MCC950-PEVs 可显著减少动脉粥样硬化斑块的形成，降低局部炎症，并抑制斑块部位的巨噬细胞和 T 细胞的增殖。我们的策略表明，PEVs 有望用于靶向递药治疗动脉粥样硬化。
