Bioinspired macrophage-targeted anti-inflammatory nanomedicine: A therapeutic option for the treatment of myocarditis

Abstract Myocarditis is a disease characterized by inflammation of the heart muscle, which increases the risk of dilated cardiomyopathy and heart failure. Macrophage migration is a major histopathological hallmark of myocarditis, making macrophages a potential therapeutic target for the management of this disease. In the present study, we synthesized a bioinspired anti-inflammatory nanomedicine conjugated with protein G (PSL-G) that could target macrophages and induce macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Notably, PSL-G exhibited a higher affinity for macrophages than non-macrophage cells. The addition of PSL-G decreased the levels of pro-inflammatory cytokines (e.g., IL-1α, IL-6, and TNF-α), but increased the level of the anti-inflammatory cytokine IL-10 in macrophages treated with lipopolysaccharide and/or interferon-γ. Furthermore, the lifetime of PSL-G in murine blood circulation was found to be significantly higher than that of PSL. Systemic injection of PSL-G into a mouse model of experimental autoimmune myocarditis remarkably reduced macrophage migration in the myocardium (16-fold compared with the positive control group) and myocardial fibrosis (8-fold). Based on these results and the fact that macrophages play a critical role in the pathogenesis of various diseases, we believe that bioinspired macrophage-targeted anti-inflammatory nanomedicines may be effective therapeutic options for the treatment of autoimmune and autoinflammatory diseases, especially myocarditis.