A metal-organic framework-based immunomodulatory nanoplatform for anti-atherosclerosis treatment
A metal-organic framework-based immunomodulatory nanoplatform for anti-atherosclerosis treatment
复制标题
DOI：
10.1016/j.jconrel.2023.01.024
复制
发表时间：
2023-01-23
影响因子：
10.8
通讯作者：
Li, Bo
中科院分区：
文献类型：
--
作者：
Xu, Zhijue;Wu, Zhaoyu;Li, Bo
免疫调节治疗已成为临床上治疗多种疾病的一种很有前途的方法。近年来，免疫调节治疗在心血管疾病的治疗中显示出良好的效果，但仍存在许多问题有待解决，如药物共递送和联合治疗的有效平台。在这项研究中，我们设计并构建了多功能纳米粒子Rapa@UiO-66-NH-FAM-IL-1 Ra（RUFI），用于治疗动脉粥样硬化性心血管疾病。这种纳米平台结合了金属有机框架（MOFs）用于药物共递送、雷帕霉素和IL 1 Ra用于免疫调节、IL-1 Ra用于细胞靶向以及5-FAM用于荧光成像的优点。RUFI具有良好的雷帕霉素和IL-1 Ra的药物释放和特异性细胞毒活性。在饮食喂养的ApoE-/-小鼠的动脉粥样硬化模型中，RUFI显著靶向并减少冠状动脉、颈动脉和动脉粥样硬化斑块。机制研究表明，RUFI调节巨噬细胞表型，细胞因子表达和自噬。这项研究表明，雷帕霉素和IL-1 Ra通过MOF载体的联合治疗增强了抗动脉粥样硬化的免疫调节作用。这种药物共递送系统表明，载有免疫调节剂的MOF载体是治疗动脉粥样硬化或其他炎症性疾病的有希望的药物。
Immunomodulatory therapy has become a promising method for the clinical treatment of many diseases. Recently, pilot studies revealed that immunomodulatory therapy exhibited good effects on the treatment of cardiovascular diseases, but many problems remain to be solved, such as useful platforms for drug co-delivery and combination therapies. In this study, we designed and constructed the multifunctional nanoparticle Rapa@UiO-66-NH-FAM-IL-1Ra (RUFI) for the treatment of atherosclerotic cardiovascular disease. This nanoplatform combined the advantages of metal-organic frameworks (MOFs) for drug co-delivery, rapamycin and IL1Ra for immunomodulation, IL-1Ra for cellular targeting, and 5-FAM for fluorescence imaging. RUFI exhibited good drug release of rapamycin and IL-1Ra and specific cytotoxicity for inflammatory macrophages in vitro. In an atherosclerotic model of diet-fed ApoE-/- mice, RUFI significantly targeted and reduced atherosclerosis plaques in coronary arteries, carotid arteries, and aortas. Mechanistic studies indicated that RUFI modulated macrophage phenotype, cytokine expression, and autophagy. This study demonstrated that combination therapy with rapamycin and IL-1Ra via MOF carriers enhanced the immunoregulatory effects against atherosclerosis. This drug codelivery system suggests that MOF carriers loaded with immunomodulators are promising treatments for atherosclerosis or other inflammatory diseases.