Ultrasound-guided and activated nanodrugs for highly selective tumor therapy

The selective eradication of cancer cells remains a primary objective in tumor therapy. To this end, tumor-targeted therapy has emerged as a key strategy to enhance drug efficacy and reduce systemic toxicity. Herein, we developed an in situ covalent targeted prodrug system that contains a coagulation targeting peptide modified nanoparticle (AMINP) and ultrasound irradiation. In this system, ultrasound-guided localized vascular disruption induces in situ generation of fibrin and the activated coagulation factor XIII (FXIIIa) within tumors. FXIIIa catalyzes the covalent crosslinking of AMINP with fibrin, enabling exceptional tumor targeting. This system is spatiotemporally controllable, relying on ultrasound to create binding targets and enhance hypoxic conditions for prodrug activation. Combined with ultrasound, AMINP achieved highly efficient tumor enrichment, increasing active drug concentration 52.1-fold versus controls and achieving 98.9% tumor suppression, with no recurrence observed in rechallenge experiments. This system establishes a robust and promising method for precision drug delivery.