Magnetic Liquid Metal Microrobots for Targeted Photothermal Therapy in Cerebrovascular Diseases

Introduction: Advances in catheter technology and embolization materials have made endovascular treatment essential for cerebrovascular diseases. However, current methods face limitations. Gallium-based liquid metals (LMs), known for their high thermal and electrical conductivity, low toxicity, and X-ray visibility. We present a magnetic 5% Fe/LM composite, engineered with thrombin, enhancing thermal conductivity, injectability, magnetic navigation, X-ray visibility, and biocompatibility. Extensive in vitro and in vivo experiments were conducted to assess its therapeutic potential for cerebrovascular diseases, focusing on targeted treatment effectiveness.

Methods: Our study approach included characterizing both thrombin-loaded and non-loaded magnetic liquid metal micro-robots, alongside in vitro cytotoxicity, hemocompatibility, and photothermal studies. We evaluated navigation, targeting, and embolization in a 3D-printed cerebrovascular model featuring a stenotic vessel and multiple aneurysms. Finally, we tested the micro-robots in rabbit aneurysm and porcine AVM models for vascular occlusion and embolization efficacy under realistic conditions, with additional testing for kidney branch embolization. Follow-up DSA and histological analysis confirmed stable embolization, with treatment safety assessed through biocompatibility and histopathology.

Results: The micro-robots showed suitable viscosity and blood compatibility. In the 3D-printed model, they were magnetically maneuverable to designated positions. In vitro cytotoxicity tests confirmed low toxicity, and showed favorable temperature control with alternating magnetic field activation. In vivo, the robots navigated antegrade and retrograde within live vessels, effectively embolizing and occluding aneurysms and malformed blood vessels. Follow-up confirmed stable occlusions, with histology revealing dense thrombus formation. Brain tissue showed no infarction, and no adverse reactions were noted in other organs.

Conclusion : Our magnetic liquid metal micro-robots achieved rapid aneurysm embolization and precise, targeted embolization of malformed vessels, addressing key limitations in treating intracranial aneurysms and cerebrovascular malformations. This approach offers a safer, more effective method for targeted interventions with potential for nanomedicine drug delivery. Additionally, the findings support targeted drug delivery for brain tumors treatable via intravascular methods. This research describes an innovative biomedical tool, providing proof of concept for targeted cerebrovascular treatment and paving the way for broader applications in precision vascular medicine.