Hybrid Polysaccharide/Magnetite Microgels for Drug-Free Magnetically Targeted Photothermal Thrombolysis.

Abstract

Cardiovascular diseases are the leading cause of death worldwide, primarily due to ischemic events caused by thrombus formation, such as ischemic heart disease and stroke. Current treatments face significant limitations: mechanical thrombectomy lacks accessibility, while fibrinolytic drugs cause severe adverse effects and show limited efficacy. Local hyperthermia may offer a broader mechanism of action, targeting not only the fibrin scaffold but also other clot components. In this work, we present a fully drug-free strategy based on hybrid microparticles (HPs) composed of magnetite nanoparticles (MNPs) assembled within cross-linked dextran microgels, for magnetically targeted photo-thermal therapy. HPs are synthesized through inverse emulsion cross-linking using biocompatible materials. They exhibit micrometer injectable size, low dispersity, high colloidal stability and excellent biocompatibility. Magnetic coupling of ≈10⁵ MNPs within each HP generates a strong magnetic macromoment (≈10^- ¹ ¹ emu), enabling efficient magnetic targeting, both in vitro and in vivo. This feature is accompanied by high photo-thermal conversion efficiency (38%). The determination of a thrombolytic temperature window enables in vitro photo-thermal thrombolysis, while in vivo application on a murine thrombus model leads to significant photo-thermal clot reduction (-32%), without any pharmaceutical agent. These findings highlight the potential of magnetically coupled magnetite nanoparticles for drug-free targeted photo-thermal thrombolysis.