Blood cell membrane camouflaged probiotic-powered micro-robot for dual-targeted thrombus therapy

Conventional thrombolytic agents exhibit significant limitations in treating thrombotic disorders characterized by narrow therapeutic windows and persistent vascular injury, failing to meet clinical requirements in terms of precision, timeliness, and treatment durability. To address these challenges, we have developed a blood cell membrane-camouflaged probiotic-powered micro-robot system (EcN-PN/rt-PA). This innovative system utilizes natural probiotics as biological carriers functionalized with drug-loaded hybrid membrane nanovesicles possessing dual-targeting capabilities against thrombus. By harnessing the rapid motility of probiotics and the active targeting properties of the hybrid membranes, the system achieves rapid and precise delivery of thrombolytic drugs to thrombotic tissues. Capitalizing on the innate rod-shaped structure and self-propelling capacity of probiotics, this micro-robot demonstrates enhanced penetration depth into thrombotic tissues, significantly improving thrombolytic efficiency. Experimental results reveal that this thrombolytic micro-robot, which combines thrombus targeting, deep penetration, and prolonged circulation characteristics, not only rapidly and accurately targets and penetrates thrombotic tissues but also extends the biological half-life of thrombolytic drugs approximately 193-fold, enabling sustained thrombolytic effects while effectively inhibiting secondary thrombus formation. This novel dual-targeting thrombolytic strategy provides an important scientific solution for treating thrombotic diseases with narrow therapeutic windows caused by vascular injury.