Thrombolytic therapy based on fucoidan-functionalized polymer nanoparticles targeting P-selectin

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Recombinant tissue plasminogen activator (rt-PA) is a standard thrombolytic agent.
• rt-PA exhibits limitations including hemorrhage risk and suboptimal efficiency.
• Targeted drug delivery systems are needed to improve rt-PA efficacy and safety.

Purpose of the Study:

• To develop and evaluate fucoidan-functionalized nanoparticles for targeted rt-PA delivery to thrombi.
• To assess the in vitro and in vivo performance of these targeted nanoparticles for thrombolysis.

Main Methods:

• Synthesis of polysaccharide-poly(isobutylcyanoacrylate) nanoparticles loaded with rt-PA and functionalized with fucoidan.
• Characterization of nanoparticle size, morphology, and rt-PA loading/release.
• In vitro validation of fibrinolytic activity and binding to P-selectin and activated platelets under flow.
• In vivo assessment of thrombolysis efficiency in a mouse model of venous thrombosis using intravital microscopy.

Main Results:

• Synthesized spherical nanoparticles with a hydrodynamic diameter of 136 ± 4 nm.
• Successfully loaded and released rt-PA from aminated nanoparticles.
• Demonstrated in vitro fibrinolytic activity and specific binding to P-selectin and platelet aggregates.
• Validated improved thrombolysis efficiency in a mouse model, evidenced by reduced platelet density.

Conclusions:

• Fucoidan-functionalized nanoparticles enhance the targeted delivery and efficacy of rt-PA.
• These nanoparticles represent a promising strategy for improving thrombolysis and mitigating associated risks.
• This study provides proof-of-concept for fucoidan-based nanocarriers in targeted thrombolysis.