Thrombolytic Therapy Based On Fucoidan-Functionalized Polymer Nanoparticles Targeting P-selectin

Maya Juenet (1) , Rachida Aid-Launais (1) , Bo Li (1) , Alice Berger (1) , Joël Aerts (2) , Antonino Nicoletti (1) , Didier Letourneur (1) , Cédric Chauvierre (1)

1 LVTS (UMR_S_1148 / U1148) - Laboratoire de Recherche Vasculaire Translationnelle
2 UMS34 FRIM - Fédération de Recherche en Imagerie Multimodalité [Paris]

Injection of recombinant tissue plasminogen activator (rt-PA) is the standard drug treatment for thrombolysis. However, rt-PA shows risk of hemorrhages and limited efficiency even at high doses. Polysaccharide-poly(isobutylcyanoacrylate) nanoparticles functionalized with fucoidan and loaded with rt-PA were designed to accumulate on the thrombus. Fucoidan has a nanomolar affinity for the P-selectin expressed by activated platelets in the thrombus. Solid spherical fluorescent nanoparticles with a hydrodynamic diameter of 136 ± 4 nm were synthesized by redox radical emulsion polymerization. The clinical rt-PA formulation was successfully loaded by adsorption on aminated nanoparticles and able to be released in vitro. We validated the in vitro fibrinolytic activity and binding under flow to both recombinant P-selectin and activated platelet aggregates. The thrombolysis efficiency was demonstrated in a mouse model of venous thrombosis by monitoring the platelet density with intravital microscopy. This study supports the hypothesis that fucoidan-nanoparticles improve the rt-PA efficiency. This work establishes the proof-of-concept of fucoidan-based carriers for targeted thrombolysis.

Domaines: Micro et nanotechnologies/Microélectronique; Cardiologie et système cardiovasculaire

Maya Juenet, Rachida Aid-Launais, Bo Li, Alice Berger, Joël Aerts, et al.. Thrombolytic Therapy Based On Fucoidan-Functionalized Polymer Nanoparticles Targeting P-selectin. Biomaterials, 2018, pp.204-216. ⟨10.1016/j.biomaterials.2017.11.047⟩. ⟨hal-02438595⟩