Di Zhang, 朱欧鸰, Fangzhi Mou, X D Wang, Chuan Cao, Wei Yi, Manyi Yang, Liu Y, DU Xinkang, X D Wang, J X Liu, D Wang, Wei Luo, Li Z, Jianguo Guan
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 Fe 3 O 4 colloidal nanocrystal clusters (p-Fe 3 O 4 @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-Fe 3 O 4 core provides a strong collective magnetic moment necessary for sequential magnetic collection (via gradient field H ) and actuation into navigating nanorobots [via precessing field H p ( t )] for targeted thrombolysis. Following thrombolysis, removal of H p ( t ) 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.