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 ·3H₂ O (17.92 wt%), thus exhibit a variable catalase-like activity against different H₂ O₂ 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.