Sialylated Macrophage Nano-Decoys Mitigate Inflammatory-ROS Microenvironment and Reprogram Endothelial Function in Myocardial Infarction

Abstract

Myocardial infarction (MI) induces the infiltration of abundant immune cells, such as macrophages, and thereby elevated inflammation characterized by elevated reactive oxygen species (ROS), which leads to dysfunction of myocardial microvessels and exacerbates myocardial ischemia and necrosis. Intravenously injected drugs hardly remain in the MI region of the heart, whereas hydrogels or cardiac patches need a complicated thoracotomy. In this study, a ROS-scavenging polyurethane nano-decoys (NDs) modified with N-acetylneuraminic acid (sialic acid, SA) (PTSA) is developed for therapy of MI via convenient intravenous injection. Due to the high affinity of SA to macrophages, PTSA is better camouflaged to avoid fast immune clearance, allowing long-term retention in the damaged myocardium. The loaded nicorandil (NIC) could be faster released in response to ROS environment, which in turn scavenged ROS and alleviated the inflammation. The NIC@PTSA effectively inhibited abnormal mitochondrial function and apoptosis of cardiomyocytes in vitro. Under the synergistic effect of ROS-scavenging and NIC release, the function of endothelial cells is reprogrammed, promoting the process of vascularization. Treatment of NIC@PTSA in vivo significantly reduced oxidative stress, promoted angiogenesis, and inhibited adverse ventricular remodeling. These multifunctional NDs provide an effective strategy for MI therapy, especially from the viewpoint of realistic application.