Ultrasound-responsive and size-transformable self-carrier nanodroplets for augmented deep vein thrombosis therapy

Deep vein thrombosis (DVT) treatment remains challenging due to the limited efficacy of conventional thrombolytic agents and the short half-lives of anticoagulants. In this study, we develop a low-molecular-weight heparin (LMWH)-functionalized, ultrasound-responsive nanodroplet with tunable size, designate as LMWH-LA@PFP. Our approach incorporates LMWH itself as an intrinsic carrier scaffold, linked to linoleic acid (LA) for self-assembly and perfluoropentane (PFP) encapsulation. This design integrates three synergistic therapeutic functions including targeted delivery, ultrasound-triggered thrombolysis, and sustained anticoagulation. After intravenous administration, LMWH selectively binds to activated platelets accumulating at the thrombus site. Ultrasound irradiation triggers PFP vaporization, driving nanodroplet expansion from nanoscale dimensions to microbubbles that subsequently collapse, mechanically disrupting the fibrin-rich thrombus matrix while enhancing drug penetration depth. Importantly, LMWH-LA fragmentations reassemble into secondary nanoparticles, thereby prolonging the duration of anticoagulant activity. The nanodroplets demonstrate robust efficacy across acute, chronic, and pregnancy-associated DVT models without evidence of fetal toxicity.