Particules activées physiquement pour une thrombolyse ciblée non pharmaceutique

Overview & Synopsis

Cardiovascular diseases remain the leading cause of death worldwide, continually fueled by population aging and lifestyle changes. Most of these fatalities are caused by ischemic events resulting from thrombus formation, such as ischemic heart disease and stroke. Current therapeutic strategies are limited: mechanical thrombectomy is not universally accessible, and fibrinolytic drugs are hindered by serious adverse effects and incomplete efficacy. This highlights the urgent need for alternative, safer, and more efficient thrombolytic approaches. Despite more than 30 years of research on nanomedicine for fibrinolytic vectorization, the promising results obtained remain mostly limited to pre-clinical studies with only a few translations to clinical trials, and still no nanoparticle-based formulation with clinical approval. Local hyperthermia may offer a broader mechanism of action, targeting not only the fibrin scaffold but also other clot components, while potentially eliminating the need for fibrinolytic drugs and their associated systemic risks. Thus, we introduced a fully drug-free photo-thermal strategy based on hybrid particles (HPs), composed of magnetite nanoparticles assembled within cross-linked dextran microgels. HPs were synthesized via inverse emulsion polymerization with biocompatible and biodegradable materials, yielding micrometer injectable size, low dispersity, high colloidal stability, and no cytotoxicity. A strong magnetic macromoment arose from the coupling of multiple individual magnetite nanoparticles within each HP, enabling magnetic activability and efficient targeting in vitro and in vivo. While this feature was accompanied by high photo-thermal conversion efficiency, the determination of a thrombolytic temperature window enabled in vitro photo-thermal thrombolysis. Importantly, significant photo-thermal clot reduction was demonstrated in a murine thrombus model, without the use of any pharmaceutical agent. Overall, these findings highlighted the value of magnetically coupling magnetite nanoparticles for drug-free targeted photo-thermal thrombolysis and demonstrated the sole contribution of thermal action on clots.