Prussian blue nanoparticles targeting multiple PANoptosome-mediated PANoptosis for myocardial ischemia-reperfusion injury therapy.

Summary

This preclinical study demonstrates that Prussian blue nanoparticles inhibit PANoptosis by binding multiple PANoptosome components, reducing pyroptosis, apoptosis, and necroptosis in myocardial ischemia-reperfusion injury. Platelet membrane-coated PB enhances cardiac targeting and improves cardiac function and remodeling, supported by multi-omics validation.

Key Findings

• PB nanoparticles bind RIPK1, ZBP1, and AIM2, disrupting PANoptosome assembly.
• Concomitant inhibition of pyroptosis, apoptosis, and necroptosis reduces MIRI injury.
• Platelet membrane-coated PB (PB@PM) enhances cardiac targeting and improves function and remodeling.
• Mechanisms include ROS scavenging, improved mitochondrial function, and restored immune-inflammatory homeostasis.
• An integrative multi-omics framework corroborated therapeutic mechanisms.

Clinical Implications

While preclinical, the PB@PM platform could inform future cardioprotective strategies during cardiac surgery, myocardial infarction, and resuscitation. Translation will require safety, dosing, and pharmacokinetic studies in large animals and early-phase trials.

Limitations

• Preclinical models; human safety, pharmacokinetics, and long-term outcomes are unknown.
• Potential nanomaterial toxicity and scalability require rigorous evaluation.

Future Directions

Conduct large-animal safety and dosing studies, define pharmacokinetics and biodistribution, and initiate phase I trials to evaluate cardioprotection in surgical and acute coronary settings.