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Platelet-Like Fusogenic Liposome-Mediated Targeting Delivery of miR-21 Improves Myocardial Remodeling by Reprogramming Macrophages Post Myocardial Ischemia-Reperfusion Injury
Advanced Science ( IF 15.1 ) Pub Date : 2021-06-17 , DOI: 10.1002/advs.202100787
Haipeng Tan 1 , Ya'nan Song 1 , Jing Chen 1 , Ning Zhang 1 , Qiaozi Wang 1 , Qiyu Li 1 , Jinfeng Gao 1 , Hongbo Yang 1 , Zheng Dong 1 , Xueyi Weng 1 , Zhengmin Wang 1 , Dili Sun 1 , Wusiman Yakufu 1 , Zhiqing Pang 2 , Zheyong Huang 1 , Junbo Ge 1
Affiliation  

Inflammatory modulations focusing on macrophage phenotype are promising candidates to promote better cardiac healing post myocardial ischemia-reperfusion (MI/R) injury. However, the peak of monocyte/macrophage recruitment is later than the time when enhanced permeability and retention effect disappears, which greatly increases the difficulty of reprogramming macrophages through systemic administration. Meanwhile, the inability of nanomaterials to release their contents to specific intracellular locations through reasonable cellular internalization pathways is another obstacle to achieving macrophage reprogramming. Here, inspired by the increase in circulating platelet-monocyte aggregates in patients′ post-MI/R and the high efficiency of fusogenic liposomes to deliver contents to the cytoplasm of target cells, a platelet-like fusogenic liposome (PLPs) is constructed. Under the coating of PLPs, mesoporous silica nanospheres with a payload of miR-21, an anti-inflammatory agent, can be specifically delivered to inflammatory monocytes in the blood circulation of MI/R induced mice. Then it directly enters the cytoplasm of monocytes through membrane fusion, thereby realizing the reparative reprogramming of the inflamed macrophages derived from it. In vivo administration of the resulting formula can effectively preserve the cardiac function of mice undergone MI/R. Minimal invasiveness and biological safety make this nano-platform a promising approach of immunotherapy.

中文翻译:

血小板样融合脂质体介导的 miR-21 靶向递送通过重编程巨噬细胞改善心肌缺血再灌注损伤后的心肌重塑

以巨噬细胞表型为重点的炎症调节有望促进心肌缺血再灌注 (MI/R) 损伤后更好的心脏愈合。然而,单核细胞/巨噬细胞募集的峰值要晚于增强的通透性和滞留效应消失的时间,这大大增加了通过全身给药重编程巨噬细胞的难度。同时,纳米材料无法通过合理的细胞内化途径将其内容物释放到特定的细胞内位置是实现巨噬细胞重编程的另一个障碍。在这里,受 MI/R 后患者循环血小板-单核细胞聚集体的增加以及融合脂质体将内容物递送至靶细胞细胞质的高效性的启发,构建了血小板样融合脂质体(PLPs)。在 PLP 涂层下,具有抗炎剂 miR-21 有效载荷的介孔二氧化硅纳米球可以特异性地递送至 MI/R 诱导小鼠血液循环中的炎性单核细胞。然后通过膜融合直接进入单核细胞的细胞质,从而实现对其衍生的炎症巨噬细胞的修复性重编程。所得配方的体内给药可以有效地保护经历MI/R的小鼠的心脏功能。微创性和生物安全性使这种纳米平台成为一种有前途的免疫治疗方法。可特异性递送至 MI/R 诱导小鼠血液循环中的炎性单核细胞。然后通过膜融合直接进入单核细胞的细胞质,从而实现对其衍生的炎症巨噬细胞的修复性重编程。所得配方的体内给药可以有效地保护经历MI/R的小鼠的心脏功能。微创性和生物安全性使这种纳米平台成为一种有前途的免疫治疗方法。可特异性递送至 MI/R 诱导小鼠血液循环中的炎性单核细胞。然后通过膜融合直接进入单核细胞的细胞质,从而实现对其衍生的炎症巨噬细胞的修复性重编程。所得配方的体内给药可以有效地保护经历MI/R的小鼠的心脏功能。微创性和生物安全性使这种纳米平台成为一种有前途的免疫治疗方法。
更新日期:2021-08-04
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