Thrombus-targeting nanosystems: Differential performance in arterial and venous circulation

The hemodynamic differences between arterial and venous systems pose significant challenges for the nanomedicine-based thrombus targeting. This study constructed three thrombus-targeting strategies: molecular recognition-based targeting, enzyme-driven chemotactic motion, and a combined targeting strategy that integrates both mechanisms. Their thrombus-targeting capability and thrombolytic efficacy were systematically compared in arterial and venous thrombus models. The results demonstrate that thrombus-targeting capability is strongly dependent on thrombus type and local hemodynamics. In venous thrombi, characterized by low flow and prolonged residence time, enzyme-driven chemotactic motion exhibited superior performance, comparable to combined targeting, owing to its active motion and chemotactic capability. In contrast, under high-flow arterial conditions, single targeting strategies failed to achieve effective retention, whereas the combined targeting strategy exhibited pronounced synergistic advantages. This study clarified the differential applicability of different targeting strategies in addressing thrombi in different hemodynamic environments, and provides insights for the rational design of precision nanomedicine delivery systems targeting more complex and heterogeneous thrombi.