Regeneration of pathological wounds,such as diabetic ulcers,poses a significant challenge in clinical settings,despite the widespread use of drugs.To overcome clinical side effects and complications,drug-free therapeu...Regeneration of pathological wounds,such as diabetic ulcers,poses a significant challenge in clinical settings,despite the widespread use of drugs.To overcome clinical side effects and complications,drug-free therapeutics need to be developed to promote angiogenesis while overcoming inflammation to restore regenerative events.This study presents a novel bioactive nanozyme based on cobalt-doped nanoglass(namely,CoNZ),which exhibits high enzymatic/catalytic activity while releasing therapeutic ions.Cobalt oxide“Co3O4”tiny crystallites produced in situ through a chemical reaction with H2O2 within CoNZ nanoparticles play a crucial role in scavenging ROS.Results showed that CoNZ-treatment to full-thickness skin wounds in mice significantly accelerated the healing process,promoting neovascularization,matrix deposition,and epithelial lining while reducing pro-inflammatory signs.Notably,CoNZ was highly effective in treating pathological wounds(streptozotocin-induced diabetic wounds).Rapid scavenging of ROS by CoNZ and down-regulation of pro-inflammatory markers while up-regulating tissue healing signs with proliferative cells and activated angiogenic factors contributed to the observed healing events.In vitro experiments involving CoNZ-cultures with macrophages and endothelial cells exposed to high glucose and ROS-generating conditions further confirmed the effectiveness of CoNZ.CoNZ-promoted angiogenesis was attributed to the release of cobalt ions,as evidenced by the comparable effects of CoNZ-extracted ionic medium in enhancing endothelial migration and tubule formation via activated HIF-1α.Finally,we compared the in vivo efficacy of CoNZ with the clinically-available drug deferoxamine.Results demonstrated that CoNZ was as effective as the drug in closing the diabetic wound,indicating the potential of CoNZ as a novel drug-free therapeutic approach.展开更多
基金supported by the National Research Foundation of Korea(2021R1A5A2022318,2018K1A4A3A01064257,2019R1A6A1 A11034536,RS-2023-00220408,2022K1A3A1A08085419,2021R1I1 A1A01049104).
文摘Regeneration of pathological wounds,such as diabetic ulcers,poses a significant challenge in clinical settings,despite the widespread use of drugs.To overcome clinical side effects and complications,drug-free therapeutics need to be developed to promote angiogenesis while overcoming inflammation to restore regenerative events.This study presents a novel bioactive nanozyme based on cobalt-doped nanoglass(namely,CoNZ),which exhibits high enzymatic/catalytic activity while releasing therapeutic ions.Cobalt oxide“Co3O4”tiny crystallites produced in situ through a chemical reaction with H2O2 within CoNZ nanoparticles play a crucial role in scavenging ROS.Results showed that CoNZ-treatment to full-thickness skin wounds in mice significantly accelerated the healing process,promoting neovascularization,matrix deposition,and epithelial lining while reducing pro-inflammatory signs.Notably,CoNZ was highly effective in treating pathological wounds(streptozotocin-induced diabetic wounds).Rapid scavenging of ROS by CoNZ and down-regulation of pro-inflammatory markers while up-regulating tissue healing signs with proliferative cells and activated angiogenic factors contributed to the observed healing events.In vitro experiments involving CoNZ-cultures with macrophages and endothelial cells exposed to high glucose and ROS-generating conditions further confirmed the effectiveness of CoNZ.CoNZ-promoted angiogenesis was attributed to the release of cobalt ions,as evidenced by the comparable effects of CoNZ-extracted ionic medium in enhancing endothelial migration and tubule formation via activated HIF-1α.Finally,we compared the in vivo efficacy of CoNZ with the clinically-available drug deferoxamine.Results demonstrated that CoNZ was as effective as the drug in closing the diabetic wound,indicating the potential of CoNZ as a novel drug-free therapeutic approach.
