Magnetic Force Enhances Pharmacologic Thrombolysis by Unlocking the "Knob-Hole" Structure of Fibrin

Thrombosis is a prevalent pathology underlying cardiovascular diseases, and pharmacologic thrombolysis is widely used in clinical. However, the dense structure of the fibrin network restricts the penetration and mobility of thrombolytic drugs within the thrombus, thereby reducing their efficiency. Disrupting the integrity of the thrombus requires high energy and generates small pieces of thrombus that increase the risk of pulmonary embolism. Here, it is demonstrated that applying a magnetic force at the pN level to unlock the "knob-hole" structure of fibrin disrupts the dense and stable mechanical state of the thrombus, consequently enhanced the efficiency of drug thrombolysis. Specifically, hollow shuttle-shaped magnetic nanoparticles are synthesized that rotate in response to an applied rotating magnetic field, generating mechanical forces to unlock the "knob-hole" structure. This led to filament disconnections within fibrin as well as exposed more binding sites for thrombolytic drugs. Meanwhile, the loaded thrombolytic drug is released at the thrombus site along with the rotation of magnetic nanoparticles. The results show that magnetic-assisted drug thrombolysis is 4.75 times more efficient than free drugs in the venous thrombosis mouse model. This non-invasive magnetic force-enhanced pharmacologic thrombolysis provides a safe and efficient thrombolysis technology and suggests external physical energies as potent biomolecular regulation means.