Bioinspired macrophage-targeted anti-inflammatory nanomedicine: A therapeutic option for the treatment of myocarditis
Bioinspired macrophage-targeted anti-inflammatory nanomedicine: A therapeutic option for the treatment of myocarditis
复制标题
仿生巨噬细胞靶向抗炎纳米药物：治疗心肌炎的一种治疗选择
DOI：
10.1016/j.msec.2021.112492
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Kang Jeong-Hun
中科院分区：
文献类型：
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作者：
Toita Riki;Kawano Takahito;Murata Masaharu;Kang Jeong-Hun
心肌炎是一种以心肌炎症为特征的疾病，它增加了扩张型心肌病和心力衰竭的风险。巨噬细胞迁移是心肌炎的主要组织病理学特征，使巨噬细胞成为治疗这种疾病的潜在靶点。在本研究中，我们合成了一种生物启发的G蛋白偶联抗炎纳米药物(PSL-G)，它可以靶向巨噬细胞，并诱导巨噬细胞从促炎的M1表型转变为抗炎的M2表型。值得注意的是，PSL-G对巨噬细胞的亲和力高于非巨噬细胞。PSL-G的加入降低了脂多糖和/或干扰素-α处理的巨噬细胞的促炎细胞因子(如IL-1α、IL-6和肿瘤坏死因子-γ)的水平，但增加了抗炎细胞因子IL-10的水平。此外，PSL-G在小鼠血液循环中的寿命显著高于PSL。在实验性自身免疫性心肌炎的小鼠模型中系统注射PSL-G显著减少了巨噬细胞在心肌中的迁移(与阳性对照组相比是16倍)和心肌纤维化(8倍)。基于这些结果和巨噬细胞在各种疾病的发病机制中起关键作用的事实，我们认为生物激发的巨噬细胞靶向抗炎纳米药物可能是治疗自身免疫性和自身炎症性疾病，特别是心肌炎的有效治疗选择。
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.