Cocklebur-inspired magnetic nanomotors for targeted thrombus therapy

Nanomotors have come to the forefront as a powerful tool for thrombolysis. Attempts in this field tend to improve the structure and function of nanomotors for safe and efficient treatment. To address the problem of low utilization and high bleeding risk, herein, we present a magnetically-driven cocklebur-like nanomotor for efficient delivery of recombinant tissue plasminogen activator (rt-PA) to treat thrombus. Composed of Fe 3 O 4 cores and spiked silicate shells, these nanomotors can rapidly respond to magnetic fields and adhere to the thrombus regardless of the blood flow impact. Besides, we use an H 2 O 2 -responsive ester to conjugate rt-PA to the nanomotors, releasing the medication only around the thrombus with abundant reactive oxygen species, thereby ensuring effective potency preservation. In vivo study proves that these cocklebur-like nanomotors can successfully treat a mouse model with a reduced thrombus area of 3.3-fold compared with direct-injection of rt-PA. Also, the coagulation system exhibits no obvious changes. All the results confirm the synergistic effect of magnetic control, adherence, and targeted drug release. These features suggest that the efficient thrombolysis ability of these nanomotors could offer new therapeutic strategies and practical value for cardiac, cerebral, and peripheral thrombotic diseases. Magnetically-driven cocklebur-like nanomotors deliver targeted thrombolytic therapy, enhancing clot dissolution and minimizing bleeding risks. • The Fe 3 O 4 cores enable the nanomotors to rapidly accumulate at targeted location. • Inspired by cocklebur's thorny structure for enhanced drug retention and adhesion. • Conjugated drug to spiny nanomotors for H 2 O 2 -responsive targeted drug delivery. • The cocklebur-inspired nanomotors exhibit higher thrombolysis efficiency and lower bleeding risk.