Authors: Dan Chen, Yifan Chen, Jianwen Liu, Xinyue Liu, Peiwen Liu, Jiabing Zhan, Zhiting Chen, Yong Gan, Mingdong Huang, Zhaoyang Chen
Published: 2025-05-02
Source: Full article
Arterial thrombosis is commonly accompanied by poor recanalization and high recurrence, typically caused by a fibrinolysis-resistant microenvironment. We identify elevated levels of plasminogen activator inhibitor–1 (PAI-1) and, notably, its strong correlation with inflammation in arterial thrombosis. To address this, small molecular inhibitors of PAI-1 and inflammation are used as bioregulators to restore vascular homeostasis. We design a carrier-free supramolecular system based on the bioregulators-tuned self-assembly of a near-infrared thrombus probe, which preferentially forms protein corona in situ to enhance plasma stability. Under acidic conditions and increased shear stress, the supramolecular assemblies disintegrate, enabling site-specific cargo release. In vivo, the probe accumulates 22.8-fold more in the thrombotic than contralateral artery. Functionally, this nanomedicine improves outcomes in mice with carotid artery thrombosis and chronic cerebral ischemia. Mechanistically, it down-regulates NF-κB signaling, inhibits NETosis and glycolysis, and up-regulates cGMP-mediated signaling, thereby alleviating inflammation and promoting fibrinolysis. This study offers an innovative codelivery strategy using supramolecular assemblies to advance therapies for arterial thrombosis.