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 macrop...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-SIRPαphagocytic 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.展开更多
基金supported by the National Natural Science Foundation of China(82202310,82170375 and 11902211)Key Research and Development Project of Science&Technology Department of Sichuan Province(2022ZDZX0020)+4 种基金Nature Science Foundation of Sichuan Province(2023NSFSC1630 and 2023NSFSC1339)1⋅3⋅5 project for disciplines of excellence-Clinical Research Fund,West China Hospital,Sichuan UniversityChina Postdoctoral Science Foundation(2022M712254)The Fundamental Research Funds for the Central Universities(2022SCU12049)Post-Doctor Research Project,West China Hospital,Sichuan University(2021HXBH068)。
文摘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-SIRPαphagocytic 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.
