NIR‐II Imaging‐Guided Self‐Penetrating Nanomotors for Millimeter‐Scale Deep Thrombolysis Tracking and Accelerated Embolus Clearance

Abstract

Abstract Pulmonary embolism (PE), a life‐threatening condition caused by thromboembolic obstruction of pulmonary arteries, demands urgent therapeutic interventions and precise diagnostic strategies to prevent systemic complications. Current thrombolytic therapies and imaging modalities face critical limitations, including hemorrhagic risks from high‐dose fibrinolytic drugs and insufficient sensitivity for detecting microemboli or dynamically tracking thrombolytic progression. Herein, a self‐propelling nanomotor platform is reported that integrates second near‐infrared window (NIR‐II) fluorescence imaging‐guided navigation, thrombus‐targeting capability, and synergistic thrombolysis for real‐time theranostics management of PE. Leveraging a relatively high fluorescence quantum yield (1.08%) for NIR‐II probes and prolonged circulation half‐life (7.2 h), these nanomotors enable sensitive detection of submillimeter microemboli and sustained, millimeter‐level precision monitoring of thrombolytic progression. Through a self‐penetration‐enhanced synergistic therapy‐ combining thermal ablation and chemical lysis, the platform achieved rapid vascular recanalization, exceeding 95% efficiency within a shortened therapeutic timeframe, using only 13.6% of the clinical urokinase (UK) dose. Validation in both the posterior auricular artery thrombosis (PAAT) and submillimeter microemboli‐induced PE models demonstrated accelerated embolus clearance, precision thrombolytic monitoring, and excellent biosafety without secondary embolism or hemorrhagic complications. This work demonstrates the significant potential of multifunctional nanomotors for the precision management of thrombotic disorders.