Hydrogen peroxide-responsive platelet membrane-coated nanoparticles for thrombus therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cardiovascular Medicine

Background:

• Thrombi cause major cardiovascular diseases, with current antithrombotic drugs facing limitations like short half-life, bleeding risks, and poor targeting.
• Hydrogen peroxide (H₂O₂) is abundant at thrombi sites, and platelets naturally target these areas, presenting opportunities for targeted therapy.

Purpose of the Study:

• To develop a H₂O₂-responsive, platelet membrane-cloaked nanoparticle loaded with argatroban (PNP_Arg) for enhanced thrombus therapy.

Main Methods:

• Synthesized a H₂O₂-degradable polymer, Poly(vanillyl alcohol-co-oxalate) (PVAX), to create an argatroban-loaded nanocore.
• Coated the nanocore with a platelet membrane to impart thrombus-targeting capabilities.
• Evaluated PNP_Arg in vitro for H₂O₂ scavenging and cellular protection, and in vivo using a mouse model of carotid arterial thrombosis.

Main Results:

• PNP_Arg demonstrated effective H₂O₂ scavenging and protected cells from H₂O₂-induced injury.
• The nanoparticles rapidly targeted thrombosed vessels and significantly suppressed thrombus formation in a mouse model.
• Reduced levels of H₂O₂ and inflammatory cytokines were observed in treated mice, with good biocompatibility.

Conclusions:

• The biomimetic PNP_Arg effectively targets thrombi, scavenges H₂O₂, and provides H₂O₂-stimulated antithrombotic action.
• This nanoparticle system represents a promising therapeutic nanomedicine for treating thrombosis diseases with enhanced efficacy and safety.