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-Fe₃O₄-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 Fe₃O₄ 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-Fe₃O₄-MO as a multifunctional platform for precise VTE management, offering non-invasive thrombolysis, real-time imaging guidance, and robust biosafety for clinical translation.