Systemic-to-local nanorobot thrombolysis.

Abstract

Magnetic micro/nanorobots hold promise for targeted thrombolysis, yet face challenges of rapid immune clearance and poor degradability, often necessitating invasive localized deployment and retrieval. Here, we present safe and versatile systemic-to-local thrombolysis enabled by magnetic nanorobots constructed from polyvinyl pyrrolidone-shielded porous Fe₃O₄ colloidal nanocrystal clusters (p-Fe₃O₄@PVP CNCs). In this building block design, the PVP coating facilitates efficient tPA (tissue plasminogen activator) loading while ensuring prolonged circulation following systemic injection. The p-Fe₃O₄ core provides a strong collective magnetic moment necessary for sequential magnetic collection (via gradient field <b>H</b>) and actuation into navigating nanorobots [via precessing field <b>H</b>_p(<i>t</i>)] for targeted thrombolysis. Following thrombolysis, removal of <b>H</b>_p(<i>t</i>) disassemble the nanorobots into dispersed CNCs that, owing to their porous structure and ultrasmall primary nanocrystals (<5 nanometers), undergo rapid lysosomal degradation and are cleared primarily via the liver-bile-intestine axis, resulting in no long-term toxicity. This platform overcomes key translational challenges for nanorobotic thrombolytic therapy.