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Hybrid Polysaccharide/Magnetite Microgels for Drug-Free Magnetically Targeted Photothermal Thrombolysis
Pierre Sarfati1, Thibault de La Taille1, Rachida Aid1,2
1Laboratory For Vascular Translational Science (LVTS), Université Paris Cité, Université Sorbonne Paris Nord, UMR-S U1148 INSERM, Paris, France.
Insights
This study introduces a novel drug-free therapy using magnetic hybrid microparticles for targeted photo-thermal treatment of blood clots. The innovative approach shows significant clot reduction in vivo without adverse effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Cardiovascular diseases are a leading global cause of death, often resulting from thrombus formation (e.g., heart attack, stroke).
- Existing treatments like mechanical thrombectomy and fibrinolytic drugs have limitations in accessibility, efficacy, and safety.
- Local hyperthermia presents a promising alternative mechanism for thrombolysis, targeting multiple clot components.
Purpose of the Study:
- To develop and evaluate a drug-free therapeutic strategy for targeted thrombolysis using magnetically guided hybrid microparticles for photo-thermal therapy.
- To assess the efficacy and biocompatibility of these hybrid microparticles in both in vitro and in vivo models.
Main Methods:
- Hybrid microparticles (HPs) were synthesized using biocompatible materials, combining magnetite nanoparticles (MNPs) within cross-linked dextran microgels.
- The HPs were characterized for size, stability, magnetic properties, and photo-thermal conversion efficiency.
- In vitro photo-thermal thrombolysis was performed, and in vivo studies utilized a murine thrombus model to evaluate clot reduction and safety.
Main Results:
- Synthesized HPs demonstrated injectable size, high colloidal stability, excellent biocompatibility, and efficient magnetic targeting due to strong magnetic macromoments.
- The HPs exhibited a high photo-thermal conversion efficiency of 38%.
- In vitro studies confirmed photo-thermal thrombolysis within a specific temperature window, and in vivo application resulted in a significant 32% reduction of thrombus in a murine model without pharmaceutical intervention.
Conclusions:
- Magnetically coupled magnetite nanoparticles within microgels offer a promising drug-free approach for targeted photo-thermal thrombolysis.
- This strategy demonstrates effective clot reduction in vivo, highlighting its potential as a safer and more accessible alternative to current cardiovascular treatments.
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.
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