PhD defense: Julie Lagouarde

Ischemic stroke accounts for the majority of cerebrovascular accidents and remains a major public health issue worldwide. Its treatment primarily relies on pharmacological thrombolysis, which consists in administering a fibrinolytic agent (t-PA, plasmin) to dissolve the clot responsible for the arterial occlusion. However, the efficacy of this therapy is limited by the slow diffusive transport of the drug toward the thrombus, especially in regions where blood flow is obstructed. In this context, the use of magnetic nanoparticles appears as a promising approach to enhance drug transport to the clot. This work presents the development of a biocompatible magnetic colloid designed to accelerate the dissolution of fibrin clots in vitro, using a microfluidic model that reproduces physiologically relevant conditions. Polyethylene glycol-functionalized iron oxide nanoparticles (NOFs@PEG) were synthesized and optimized to combine colloidal stability in a simplified biological medium (PBS) with magnetic responsiveness. Under a rotating magnetic field, the NOFs@PEG self- assemble into elongated, micron-sized aggregates that rotate synchronously with the applied field. This collective motion generates local recirculation flows in the occluded channel, significantly enhancing the dissolution of fibrin clots by plasmin compared with passive diffusion. Under optimal conditions, the degradation rate was up to 9.6 times faster than in the absence of a magnetic field. Cytotoxicity assays confirmed the biocompatibility of NOFs@PEG, with cell viability remaining above 80%.
Overall, this study demonstrates the feasibility and robustness of a magnetically assisted thrombolysis strategy capable of overcoming the diffusional limitations of fibrinolytic agents, providing a solid foundation for the future development of improved therapeutic approaches for ischemic stroke.