Dual Frequency-Regulated\nMagnetic Vortex Nanorobots\nEmpower Nattokinase for Focalized Microvascular Thrombolysis

Magnetic nanorobots are emerging players in thrombolytic\ntherapy\ndue to their noninvasive remote actuation and drug loading capabilities.\nAlthough the nanorobots with a size under 100 nm are ideal to apply\nin microvascular systems, the propulsion performance of nanorobots\nis inevitably compromised due to the limited response to magnetic\nfields. Here, we demonstrate a nattokinase-loaded magnetic vortex\nnanorobot (NK-MNR) with an average size around 70 nm and high saturation\nmagnetization for mechanical propelling and thermal responsive thrombolysis\nunder a magnetic field with dual frequencies. The nanorobots are stable\nin suspension and undergo the magneto-steered assembly into chain-like\nNK-MNRs, which are regulated to generate magnetic forces to mechanically\ndamage and penetrate the thrombus by the low-frequency rotating magnetic\nfield. Synergistically, enhanced magnetic hyperthermia is triggered\nby an alternating magnetic field of high frequency, enabling heat-induced\nNK release and fibrinolysis. In this dual frequency-regulated magnetothrombolysis\n(fRMT) strategy, nanorobots collaborate under the dual magnetic energy\nconversion model to achieve the vasculature recanalization rate of\n81.0% in thrombotic mice. Overall, the nanorobot with the special\nmagnetic vortex property and multimodel controls is a promising nanoplatform\nfor <i>in vivo</i> focalized microvascular thrombolysis.