Platelet‐Like Fusogenic Liposome‐Mediated Targeting Delivery of miR‐21 Improves Myocardial Remodeling by Reprogramming Macrophages Post Myocardial Ischemia‐Reperfusion Injury

Abstract

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.

Periodontitis Is Associated With Heart Failure: A Population-Based Study (NHANES III)

“…In addition to cardiovascular diseases such as ischemic heart disease, hypertension, and arrhythmia, inflammation also plays an important role in heart failure ( Pieske et al, 2019 ; Groenewegen et al, 2020 ; Schiattarella et al, 2020 ). Studies have shown that inflammatory factors can lead to ventricular remodeling, which in turn affects the development of heart failure ( Al-Taweel et al, 2017 ; Tan et al, 2021 ; Yan et al, 2021 ). In addition, there are also animal studies and clinical studies focusing on the positive effects of anti-inflammatory treatments on cardiovascular diseases ( Bäck and Hansson, 2015 ; Huang and Frangogiannis, 2018 ; Ma et al, 2019 ; Gao et al, 2021 ).…”

Macrophage-targeting gene silencing orchestrates myocardial microenvironment remodeling toward the anti-inflammatory treatment of ischemia-reperfusion (IR) injury

“…The in vivo macrophage targeting of Cy5-siRNA-containing NCs was further explored via flow cytometry. In the early stage of reperfusion (several hours to several days after IR), pro-inflammatory M1-type macrophages occupy a greatly larger proportion than anti-inflammatory M2-type macrophages in the injured myocardium [ [58] , [59] , [60] , [61] ]. Thus, the proportion of M1-or M2-type macrophages in the injured heart and the internalization of Cy5-siRNA-containing NCs in them were monitored.…”

Exosomes Derived From Mesenchymal Stem Cells: Novel Effects in the Treatment of Ischemic Stroke

“… Shi et al (2018) identified that miR-21, an exosome derived from MSCs, down-regulated the expression of PTEN by activating the PI3K/AKT signaling pathway, thereby protecting cardiomyocytes from death induced by ischemia and oxidative stress. In addition, the latest study found that miRNA-21 can also improve myocardial remodeling after myocardial ischemia-reperfusion injury by reprogramming macrophages ( Tan et al, 2021 ). Reprogrammed macrophages coordinate the remodeling of the myocardial microenvironment in the anti-inflammatory treatment of ischemia reperfusion (IR) injury ( Tan et al, 2021 ).…”

“…In addition, the latest study found that miRNA-21 can also improve myocardial remodeling after myocardial ischemia-reperfusion injury by reprogramming macrophages ( Tan et al, 2021 ). Reprogrammed macrophages coordinate the remodeling of the myocardial microenvironment in the anti-inflammatory treatment of ischemia reperfusion (IR) injury ( Tan et al, 2021 ). MiR-30c-5p can down-regulate BCL2-like 11 (BCL2L11) to improve myocardial injury, histopathological changes and apoptosis in rat I/R model ( Meng et al, 2021 ).…”