Dual delivery of an NF- κ B inhibitor and IL-10 through supramolecular hydrogels polarizes macrophages and promotes cardiac repair after myocardial infarction
Dual delivery of an NF- κ B inhibitor and IL-10 through supramolecular hydrogels polarizes macrophages and promotes cardiac repair after myocardial infarction
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DOI：
10.1016/j.actbio.2023.03.035
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发表时间：
2023-05-26
影响因子：
9.7
通讯作者：
Zhang，Ye
中科院分区：
文献类型：
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作者：
Wang，Di;Hu，Yang;Zhang，Ye
使用抗炎策略有可能成为心肌梗死（MI）后心室重塑的决定性治疗。抗炎药对巨噬细胞表型的调节有助于减轻心肌纤维化。然而，他们的保留率低，严重影响治疗效果。在这里，我们提出了一种超分子化合物，NapFFY，与IL-10和SN 50共组装作为一种新的抗炎SN 50/IL-10/NapFFY水凝胶具有心脏保护性能。体外实验和大鼠体内实验结果表明，SN 50/IL-10/NapFFY水凝胶具有理想的IL-10和SN 50缓释效果。在MI大鼠模型中心肌内注射SN 50/IL-10/NapFFY水凝胶显著抑制促炎细胞因子的表达。它促进M2巨噬细胞的极化，从而减少心肌细胞凋亡并改善边缘区的血管化。具体而言，SN 50/IL-10/NapFFY水凝胶显著改善了MI后28天的心脏功能并改善了心室重塑。SN 50/IL-10/NapFFY水凝胶有望成为一种新的抗炎药物，用于心肌梗死的临床治疗。抗炎是治疗心肌梗死后心室重构的理想策略。SN 50和IL-10已被证明分别在炎症过程中具有不同的作用。然而，直接静脉内施用或心肌内注射SN 50或IL-10不是可行的选择，因为其体内半衰期差。本研究旨在评价负载NF-κB抑制剂（SN 50）和IL-10的超分子水凝胶的协同心脏保护作用。动物实验表明，SN 50/IL-10/NapFFY水凝胶改善了大鼠MI模型中的炎症微环境，改善了梗死区的心功能。我们预期SN 50/IL 10 NapFFY水凝胶可在不久的将来用于临床治疗MI。
The use of anti-inflammatory strategies has the potential to be a definitive treatment for ventricular remodeling post myocardial infarction (MI). The regulation of macrophage phenotypes by anti-inflammatory agents contributes to the alleviation of myocardial fibrosis. However, their poor retention rates severely affect treatment efficacy. Here, we propose a supramolecular compound, NapFFY, to co-assemble with IL-10 and SN50 as a novel anti-inflammatory SN50/IL-10/NapFFY hydrogel with cardioprotective properties. Results from thein vitroandin vivoexperiments in murine cell line and rats, respectively, demonstrated that the SN50/IL-10/NapFFY hydrogel exhibits an ideal and sustained release of IL-10 and SN50. Intramyocardial injection of the SN50/IL-10/NapFFY hydrogel in a rat model of MI significantly inhibited the expression of proinflammatory cytokines. It promoted the polarization of M2 macrophages, which reduced cardiomyocyte apoptosis and improved vascularization at the border zones. Specifically, the SN50/IL-10/NapFFY hydrogel significantly improved heart function and ameliorated ventricular remodeling 28 days post MI. We envision that the SN50/IL-10/NapFFY hydrogel could serve as a new anti-inflammatory agent for the clinical treatment of MI in future studies.Statement of significanceAnti-inflammation is an ideal strategy for the treatment of ventricular remodeling post myocardial infarction (MI). SN50 and IL-10 have been shown to have diverse roles in antiinflammatory process, respectively. However, direct intravenous administration or intramyocardial injection of SN50 or IL-10 is not a viable option given its poor half-lifein vivo. This study aimed to evaluate the synergistic cardioprotective effects of a supramolecular hydrogel loaded with an NF-κB inhibitor (SN50) and IL-10. Animal experiments showed that the SN50/IL-10/NapFFY hydrogels ameliorated the inflammatory microenvironment, and improved cardiac function to the infarct area in a rat model of MI. We anticipate that SN50/IL10NapFFY hydrogel could be used clinically to treat MI in the near future.