CRISPR-Cas9 cleaves DNA microspheres to release drug for efficient thrombosis treatment

The drug delivery nanocarriers are widely employed in thrombolytic therapy. However, the off targeting and ineffective drug release of delivery vehicles make it difficult to targeted accumulation, effective diffusion, and penetration into thrombus tissue. Herein, we reported a biocompatible magnetic microsphere constructed via a programmable DNA rolling circle amplification (RCA) reaction integrated with iron oxide magnetic nanoparticles (Fe₃O₄ NPs). By combining ultrasound and photoacoustic imaging for diagnosis with magnetic field-guided targeting for therapy, these magnetic DNA microspheres were further functionalized with CRISPR-Cas9 to enable precise regulation of thrombolytic drug release. This system promotes deep penetration into thrombi and enhances mass transfer within clots, thereby accelerating thrombolysis. As a result, the thrombolytic drug, tissue plasminogen activator (tPA), can be delivered selectively to thrombus sites, where it is rapidly released and penetrates the clot, significantly improving the thrombolytic rate and therapeutic efficacy.