用于心肌梗死治疗的具有活性氧清除活性的锌基纳米酶可注射多功能水凝胶的设计
Design of a Zn-based nanozyme injectable multifunctional hydrogel with ROS scavenging activity for myocardial infarction therapy.
作者信息
Zhong Yiming, Yang Yi, Xu Yuze, Qian Bei, Huang Shixing, Long Qiang, Qi Zhaoxi, He Xiaojun, Zhang Yecen, Li Lihui, Hai Wangxi, Wang Xinming, Zhao Qiang, Ye Xiaofeng
机构信息
Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
College of Chemistry and Materials Science, Shanghai Normal University, Shanghai, 200234, China.
出版信息
Acta Biomater. 2024 Mar 15;177:62-76. doi: 10.1016/j.actbio.2024.01.015. Epub 2024 Jan 17.
The existing strategies for myocardial infarction therapy mainly focus on reinstating myocardial blood supply, often disregarding the intrinsic and intricate microenvironment created by elevated levels of reactive oxygen species (ROS) that accompanies myocardial infarction. This microenvironment entails cardiomyocytes apoptosis, substantial vascular cell death, excessive inflammatory infiltration and fibrosis. In such situation, the present study introduces a zinc-based nanozyme injectable multifunctional hydrogel, crafted from ZIF-8, to counteract ROS effects after myocardial infarction. The hydrogel exhibits both superoxide dismutase (SOD)-like and catalase (CAT)-like enzymatic activities, proficiently eliminating surplus ROS in the infarcted region and interrupting ROS-driven inflammatory cascades. Furthermore, the hydrogel's exceptional immunomodulatory ability spurs a notable transformation of macrophages into the M2 phenotype, effectively neutralizing inflammatory factors and indirectly fostering vascularization in the infarcted region. For high ROS and demanding for zinc of the infarcted microenvironment, the gradual release of zinc ions as the hydrogel degrades further enhances the bioactive and catalytic performance of the nanozymes, synergistically promoting cardiac function post myocardial infarction. In conclusion, this system of deploying catalytic nanomaterials within bioactive matrices for ROS-related ailment therapy not only establishes a robust foundation for biomedical material development, but also promises a holistic approach towards addressing myocardial infarction complexities. STATEMENT OF SIGNIFICANCE: Myocardial infarction remains the leading cause of death worldwide. However, the existing strategies for myocardial infarction therapy mainly focus on reinstating myocardial blood supply. These therapies often ignore the intrinsic and intricate microenvironment created by elevated levels of reactive oxygen species (ROS). Hence, we designed an injectable Zn-Based nanozyme hydrogel with ROS scavenging activity for myocardial infarction therapy. ALG-(ZIF-8) can significantly reduce ROS in the infarcted area and alleviate the ensuing pathological process. ALG-(ZIF-8) gradually releases zinc ions to participate in the repair process and improves cardiac function. Overall, this multifunctional hydrogel equipped with ZIF-8 makes full use of the characteristics of clearing ROS and slowly releasing zinc ions, and we are the first to test the therapeutic efficacy of Zinc-MOFs crosslinked-alginate hydrogel for myocardial infarction.
现有的心肌梗死治疗策略主要集中在恢复心肌血液供应上,常常忽视了伴随心肌梗死出现的活性氧(ROS)水平升高所产生的内在且复杂的微环境。这种微环境会导致心肌细胞凋亡、大量血管细胞死亡、过度的炎症浸润和纤维化。在这种情况下,本研究引入了一种由ZIF-8制备的基于锌的纳米酶可注射多功能水凝胶,以对抗心肌梗死后的ROS效应。该水凝胶具有超氧化物歧化酶(SOD)样和过氧化氢酶(CAT)样的酶活性,能够有效清除梗死区域多余的ROS,并中断ROS驱动的炎症级联反应。此外,水凝胶卓越的免疫调节能力促使巨噬细胞显著转变为M2表型,有效中和炎症因子并间接促进梗死区域的血管生成。对于梗死微环境中高ROS且对锌有需求的情况,随着水凝胶降解锌离子的逐渐释放进一步增强了纳米酶的生物活性和催化性能,协同促进心肌梗死后的心脏功能。总之,这种在生物活性基质中部署催化纳米材料用于ROS相关疾病治疗的系统不仅为生物医学材料的开发奠定了坚实基础,也为解决心肌梗死的复杂性提供了一种全面的方法。重要性声明:心肌梗死仍然是全球范围内主要的死亡原因。然而,现有的心肌梗死治疗策略主要集中在恢复心肌血液供应上。这些疗法往往忽略了活性氧(ROS)水平升高所产生的内在且复杂的微环境。因此,我们设计了一种具有ROS清除活性的可注射锌基纳米酶水凝胶用于心肌梗死治疗。ALG-(ZIF-8)能够显著降低梗死区域的ROS并减轻随之而来的病理过程。ALG-(ZIF-8)逐渐释放锌离子参与修复过程并改善心脏功能。总体而言,这种配备ZIF-8的多功能水凝胶充分利用了清除ROS和缓慢释放锌离子的特性,并且我们首次测试了锌-金属有机框架交联藻酸盐水凝胶对心肌梗死的治疗效果。