New diagnostic and therapeutic strategies for myocardial infarction via nanomaterials

Abstract

Myocardial infarction is lethal to patients because of insufficient blood perfusion to vital organs. Several attempts have been made to improve its prognosis, among which nanomaterial research offers an opportunity to address this problem at the molecular level and has the potential to improve disease prevention, diagnosis, and treatment significantly. Up to now, nanomaterial-based technology has played a crucial role in broad novel diagnostic and therapeutic strategies for cardiac repair. This review summarizes various nanomaterial applications in myocardial infarction from multiple aspects, including high precision detection, pro-angiogenesis, regulating immune homeostasis, and miRNA and stem cell delivery vehicles. We also propose promising research hotspots that have not been reported much yet, such as conjugating pro-angiogenetic elements with nanoparticles to construct drug carriers, developing nanodrugs targeting other immune cells except for macrophages in the infarcted myocardium or the remote region. Though most of those strategies are preclinical and lack clinical trials, there is tremendous potential for their further applications in the future.

Keywords: Cardiac biomarker; Ischaemic heart disease; Myocardial infarction; Nano-delivery system; Nanomaterials; New diagnostic and therapeutic strategies.

Figure 1

The schematic diagram shows the application of nanomaterials in MI. Nanomaterials help lower the detective limit of cardiac biomarkers, thus enabling a timely recognition of potential patients. In basic research, Nanomaterials have been explored to promote angiogenesis and regulate immune responses after MI. They also played a promising role in delivering novel biomolecules like miRNA and stem cells.

Figure 2

Schematic illustration of how copper promotes angiogenesis. The pro-angiogenetic signaling pathway affected by copper is the regulation of HIF-1α degradation, where copper inhibits the hydroxylation of prolyl residues to maintain the intracellular concentration of active HIF-1α. Copper also influences the combination between HIF-1 transcriptional complex and HRE sites. It was also speculated that copper also directly actives HIF-1α via downregulating the expression of GSK-3β. Abbreviations: HIF: hypoxia-inducible facto; PHD: prolyl hydroxylase domain-containing protein; VHF: von Hippel–Lindau protein; GSK-3β: glycogen synthase kinase-3β; CBP: CREB-binding protein; the red straight line with arrow means activation; the green straight line with straight-arrow means inhibition; the green truncated line with straight-arrow means inhibition under speculation.

Figure 3

Schematic illustration of cerium nanoparticles in pro-angiogenesis. The redox cycling on the surface of cerium nanoparticles helps remove intracellular ROS to maintain the mitochondrial membrane potential and inhibit apoptosis of endothelial cells. It was also assumed that cerium nanoparticles could absorb intracellular oxygen, thus the induced hypoxia environment protected HIF-1α from degradation. Another pro-angiogenetic mechanism proposed was that cerium nanoparticles also upregulated Ref-1α that reduced oxidized cysteine residues in HIF-1α to enhance the expression of VEGF. Abbreviations: MMP: mitochondrial membrane potential; HIF: hypoxia-inducible facto; PHD: prolyl hydroxylase domain-containing protein; VHF: von Hippel–Lindau protein; Ref-1α: reduction-oxidation factor 1; CBP: CREB-binding protein; the red straight line with an arrow means activation; the green straight line with a straight arrow means inhibition.

Figure 4

Regarding the biodegradation-susceptible of miRNAs and stem cells compared to other biomolecules in vivo, the in-situ injection is applied to enhance drug delivery efficacy. However, this approach decreases the possibility of clinical translation since the in-situ injection induces a second injury to the damaged fragile myocardium.