Construction and application of therapeutic metal-polyphenol capsule for peripheral artery disease
Construction and application of therapeutic metal-polyphenol capsule for peripheral artery disease
复制标题
治疗外周动脉疾病的金属多酚胶囊的构建及应用
DOI：
10.1016/j.biomaterials.2020.120199
复制
发表时间：
2020-10-01
期刊：
影响因子：
14
通讯作者：
Yang, Jing
中科院分区：
文献类型：
--
作者：
Duan, Jianwei;Chen, Zuoguan;Yang, Jing
外周动脉疾病（PAD）患者的病变处于有害的微环境中，其特征是氧化应激和炎症浸润增加。因此，必须沿着血管生成改善微环境。在这项研究中，金属多酚胶囊（Cu-EGCG），它结合了治疗抗炎和抗氧化活性的表没食子儿茶素没食子儿茶素没食子酸酯（EGCG）和铜离子的血管生成活性，通过EGCG和铜离子之间的协调。在体外证明了铜离子从Cu-EGCG中的持续释放，并且生物相容性Cu-EGCG可以抑制细胞内ROS，在存在细胞毒性水平的ROS的情况下减少细胞死亡，并降低促炎细胞因子（TNF-α，IL-6）的表达。此外，Cu-EGCG诱导血管内皮生长因子（VEGF）的分泌在后肢缺血模型的PAD。更重要的是，在缺血组织中血小板内皮细胞粘附分子-1（CD 31）和增殖细胞核抗原（PCNA）的表达上调，表明Cu-EGCG对血管生成的显着影响。此外，Cu-EGCG在缺血后肢中显示出显著的血液恢复。综上所述，具有生物相容性和治疗功能的Cu-EGCG在PAD治疗中具有巨大的应用潜力。
Lesions of patients with peripheral artery disease (PAD) are in a harmful microenvironment, which features increased oxidative stress and inflammatory infiltration. Hence, it is essential to improve the microenvironment along with angiogenesis. In this study, metal-polyphenol capsules (Cu-EGCG), which combines the therapeutic anti-inflammatory and antioxidant activities of EGCG and the angiogenic activity of copper ions, were synthesized through coordination between EGCG and copper ions. The sustained release of the copper ions from Cu-EGCG was demonstrated in vitro, and biocompatible Cu-EGCG can scavenge intracellular ROS, reduce cell death in the presence of cytotoxic levels of ROS, and decrease the expression of pro-inflammatory cytokines (TNF-alpha, IL-6). Moreover, Cu-EGCG induced the secretion of vascular endothelial growth factor (VEGF) in a hindlimb ischaemia model of PAD. More importantly, the upregulated expression of platelet endothelial cell adhesion molecule-1 (CD31) and proliferating cell nuclear antigen (PCNA) in ischaemic tissues indicated the remarkable effect of Cu-EGCG on angiogenesis. In addition, Cu-EGCG showed significant blood recovery in ischaemic hindlimbs. Taking these results together, biocompatible Cu-EGCG with therapeutic functions holds great potential applications for PAD therapy.