Designer Functional Nanomedicine for Myocardial Repair by Regulating the Inflammatory Microenvironment

Abstract

Acute myocardial infarction is a major global health problem, and the repair of damaged myocardium is still a major challenge. Myocardial injury triggers an inflammatory response: immune cells infiltrate into the myocardium while activating myofibroblasts and vascular endothelial cells, promoting tissue repair and scar formation. Fragments released by cardiomyocytes become endogenous “danger signals”, which are recognized by cardiac pattern recognition receptors, activate resident cardiac immune cells, release thrombin factors and inflammatory mediators, and trigger severe inflammatory responses. Inflammatory signaling plays an important role in the dilation and fibrosis remodeling of the infarcted heart, and is a key event driving the pathogenesis of post-infarct heart failure. At present, there is no effective way to reverse the inflammatory microenvironment in injured myocardium, so it is urgent to find new therapeutic and diagnostic strategies. Nanomedicine, the application of nanoparticles for the prevention, treatment, and imaging of disease, has produced a number of promising applications. This review discusses the treatment and challenges of myocardial injury and describes the advantages of functional nanoparticles in regulating the myocardial inflammatory microenvironment and overcoming side effects. In addition, the role of inflammatory signals in regulating the repair and remodeling of infarcted hearts is discussed, and specific therapeutic targets are identified to provide new therapeutic ideas for the treatment of myocardial injury.

KLF9 deficiency protects the heart from inflammatory injury triggered by myocardial infarction

“…The inflammatory response is thought to be involved in the pathogenesis of MI, coordinating beneficial homeostatic responses in the heart to promote cardiac repair after MI [ 17 ]. The innate immune cells which are recruited into myocardial tissue mediated the clearance of necrotic cardiomyocytes through phagocytosis after MI [ 18 ].…”

Control of the post-infarct immune microenvironment through biotherapeutic and biomaterial-based approaches

“…While therapeutics alone are clearly efficacious tools for reorientation of the post ischemic inflammatory milieu, their use can be hindered by factors such as suboptimal pharmacokinetics (i.e., rapid blood clearance, non-specific cell and tissue biodistribution) and resulting off-target effects such as systemic toxicity and increased risk of infection [ 263 ]. Functional biomaterials have been widely used to address these challenges in cardiac repair [ 264 , 265 ], which may be composed of either natural or synthetic components (Table 3 ). Here, we outline biomaterial-based strategies, including systemically or locally administered therapeutic vehicles that have demonstrated utility in modulating the immune response to mitigate impacts toward IHF.…”

Engineered extracellular vesicles as intelligent nanosystems for next-generation nanomedicine

“…[194][195][196][197][198] Other diseases such as cardiovascular, inflammatory, neurodegenerative, and infectious diseases are also accompanied by changes in various physiological parameters, providing the possibility of endogenous stimulus-response therapy. [199][200][201] pH stimuli-responsive EVs. Most tumor cells have reprogrammed their glucose metabolism to enable their rapid proliferation.…”

“…194–198 Other diseases such as cardiovascular, inflammatory, neurodegenerative, and infectious diseases are also accompanied by changes in various physiological parameters, providing the possibility of endogenous stimulus–response therapy. 199–201…”