Redox Modulatory Cu(II)‐Baicalein Microflowers Prepared in One Step Effectively Promote Therapeutic Angiogenesis in Diabetic Mice

Reactive oxygen species (ROS) have been implicated in multiple cellular processes, and an imbalance in redox homeostasis gives rise to diseases, therefore, reestablishing redox homeostasis is a way to cure. Here, copper‐based metal‐organic networks (Cu‐MON) are generated by one‐step reaction using anti‐inflammatory and antioxidant baicalein as organic ligand and pro‐angiogenic copper as metal ions. Phosphate buffered saline is required for triggering Cu‐MON formation, and baicalein regulates the morphology and particle size of Cu‐MON. Cu‐MON are composed of Cu‐baicalein complexes (82.08 wt%) and Cu3(PO4)2·3H2O (17.92 wt%), thus exhibit a variable catalase‐like activity against different H2O2 levels due to the reversible change between Cu2+/Cu1+/Cu0 species. Intramuscular injection of Cu‐MON significantly increases blood flow of ischemic limb in diabetic mice, enhances the relative activities of redox‐related enzymes in ischemic muscle, thus effectively ameliorating the oxidative damage. Taken together, through moderate and dynamic “precise homeostasis regulation of cells,” Cu‐MON can be an efficient therapeutic strategy for peripheral arterial disease with diabetic complications. By a simple one‐step process, Cu(II)‐organic coordination microflowers are prepared, which dynamically regulate redox homeostasis through the reversible oxidation state change of copper ions and its effect on the activities of oxidases and antioxidant enzymes. Blood flow is significantly restored in diabetic mice with critical limb ischemia after treating with copper‐based metal‐organic networks.