Doping-Engineered Proangiogenic Nanozymes Orchestrate Ischemic Tissue Regeneration via Cytoprotection and...

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Regenerative Medicine

Background:

• Ischemic diseases necessitate both reperfusion and protection against secondary injuries, such as oxidative stress.
• Current therapies often lack integrated approaches for tissue protection and regeneration.
• Nanozymes offer potential for catalytic antioxidant activity but often lack regenerative capabilities.

Purpose of the Study:

• To introduce the concept of "proangiogenic nanozymes" for integrated ischemic disease therapy.
• To develop and screen nanozymes doped with angiogenic elements for enhanced therapeutic effects.
• To evaluate the efficacy of the lead candidate, copper-doped Prussian blue (CuPB), in preclinical models.

Main Methods:

• Doping Prussian blue nanozymes with various angiogenic elements (Mg, Co, Cu, Zn, Sr, Eu).
• Systematic assessment of catalytic antioxidant activity and proangiogenic performance.
• Evaluation of CuPB in murine models of hind limb ischemia and myocardial infarction.

Main Results:

• Copper-doped Prussian blue (CuPB) demonstrated potent antioxidant activity, decomposing reactive oxygen species and reducing apoptosis.
• CuPB significantly stimulated angiogenesis, promoting vascular repair and tissue regeneration.
• CuPB showed therapeutic benefits in both hind limb ischemia and myocardial infarction models following local and systemic administration.

Conclusions:

• Proangiogenic nanozymes, exemplified by CuPB, offer a dual-action therapeutic strategy for ischemic diseases.
• CuPB effectively mitigates oxidative stress and promotes vascular repair, demonstrating significant translational potential.
• This approach integrates catalytic nanomedicine with vascular regeneration for enhanced ischemic tissue recovery.