Dual Frequency-Regulated Magnetic Vortex Nanorobots Empower Nattokinase for Focalized Microvascular Thrombolysis

Magnetic nanorobots are emerging players in thrombolytic therapy due to their noninvasive remote actuation and drug loading capabilities. Although the nanorobots with a size under 100 nm are ideal to apply in microvascular systems, the propulsion performance of nanorobots is inevitably compromised due to the limited response to magnetic fields. Here, we demonstrate a nattokinase-loaded magnetic vortex nanorobot (NK-MNR) with an average size around 70 nm and high saturation magnetization for mechanical propelling and thermal responsive thrombolysis under a magnetic field with dual frequencies. The nanorobots are stable in suspension and undergo the magneto-steered assembly into chain-like NK-MNRs, which are regulated to generate magnetic forces to mechanically damage and penetrate the thrombus by the low-frequency rotating magnetic field. Synergistically, enhanced magnetic hyperthermia is triggered by an alternating magnetic field of high frequency, enabling heat-induced NK release and fibrinolysis. In this dual frequency-regulated magnetothrombolysis (fRMT) strategy, nanorobots collaborate under the dual magnetic energy conversion model to achieve the vasculature recanalization rate of 81.0% in thrombotic mice. Overall, the nanorobot with the special magnetic vortex property and multimodel controls is a promising nanoplatform for in vivo focalized microvascular thrombolysis.