Multimodal Imaging and Therapeutic Effects of Targeted Phase Change Nanoparticles in Venous Thromboembolism

ABSTRACT Venous thromboembolism (VTE) remains a critical clinical challenge due to limitations in conventional therapies, including poor thrombus targeting, inadequate imaging, and bleeding risks. This study develops nanoparticles composed of polylactic‐co‐glycolic acid, perfluoropentane, ferric oxide, and a macrophage membrane (designated as PLGA‐PFP‐Fe 3 O 4 ‐MO NPs) for targeted thrombolysis and dual‐modal imaging. The NPs integrate macrophage membrane coating to enhance immune evasion and thrombus targeting, a perfluoropentane core enabling phase‐change capabilities under low‐intensity focused ultrasound (LIFU), and Fe 3 O 4 for magnetic targeting and photoacoustic imaging. Evaluations in vitro and in a rat deep vein thrombosis model demonstrate superior thrombolytic efficacy, imaging performance, and long‐term safety. The NPs reduce residual thrombus area to 15.57%, outperforming urokinase at 30.25% and low‐molecular‐weight heparin, while restoring venous blood flow and eliminating pulmonary embolism incidence. Long‐term safety assessments over 28 days confirm no systemic toxicity or organ damage. LIFU‐triggered phase transitions enable contrast‐enhanced ultrasound imaging with prolonged durability exceeding 8 min surpassing SonoVue, and high‐resolution photoacoustic localization. These findings establish PLGA‐PFP‐Fe 3 O 4 ‐MO as a multifunctional platform for precise VTE management, offering non‐invasive thrombolysis, real‐time imaging guidance, and robust biosafety for clinical translation.