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<p>Deep vein thrombosis (DVT) is a serious medical condition that can lead to life-threatening complications. Conventional or nanotechnology-based antithrombotic therapies frequently lead to incomplete thrombolysis and may result in DVT recurrence. Emerging evidence highlights that the persistent neutrophil extracellular traps (NETs) scaffold synergistically interacts with reactive oxygen species overproduction and inflammatory cascades, collectively compromising thrombus resolution and establishing a prothrombotic microenvironment for recanalization failure. Hence, in response to this pathomechanism, a bismuth (Bi)-based nanoplatform (PSA@Bi-TNK-HCQ; PBTH) was constructed. PBTH nanoparticles (NPs) were delivered in a targeted manner to activated endothelial cells via polysialic acid (PSA) and enabled thrombus visualization through dual-energy computed tomography imaging. Therapeutically, a dual-drug antithrombotic effect was achieved through the breakdown of fibrin by tenecteplase (TNK) and the inhibition of NET structures by hydroxychloroquine (HCQ). This mechanistically complementary approach showed superior thrombolytic performance in vivo compared to monotherapy, with a residual thrombus rate of 18.7%. Furthermore, the multienzyme-like activities of PBTH NPs restored endothelial function by mitigating oxidative stress damage and inflammation, thereby preventing thrombus recurrence and pulmonary embolism. The vicious cycle of NET-mediated thrombosis-associated immune dysregulation, a locally abnormal thrombotic microenvironment, and endothelial dysfunction was ultimately broken. This work provides a promising two-pronged approach to the treatment of DVT by increasing the effectiveness of thrombolysis while reducing the risk of reocclusion.</p> Graphical Abstract <p></p>

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A bismuth-based nanoplatform with synergistic fibrin/NET disruption and antioxidant/anti-inflammatory capabilities for enhanced thrombolysis and prevention of deep vein thrombosis recurrence

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月26日

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  • Lian Xu,
  • Jiangwei Chen,
  • Wenli Zhang,
  • Qianying Du,
  • Xin Huang,
  • Ying Luo,
  • Yi Wang,
  • Sijin Chen,
  • Xiyue Rong,
  • Jia Liu,
  • Zhongsheng Xu,
  • Haitao Ran,
  • Yun Liu,
  • Dajing Guo,
  • Jie Xu

摘要

Deep vein thrombosis (DVT) is a serious medical condition that can lead to life-threatening complications. Conventional or nanotechnology-based antithrombotic therapies frequently lead to incomplete thrombolysis and may result in DVT recurrence. Emerging evidence highlights that the persistent neutrophil extracellular traps (NETs) scaffold synergistically interacts with reactive oxygen species overproduction and inflammatory cascades, collectively compromising thrombus resolution and establishing a prothrombotic microenvironment for recanalization failure. Hence, in response to this pathomechanism, a bismuth (Bi)-based nanoplatform (PSA@Bi-TNK-HCQ; PBTH) was constructed. PBTH nanoparticles (NPs) were delivered in a targeted manner to activated endothelial cells via polysialic acid (PSA) and enabled thrombus visualization through dual-energy computed tomography imaging. Therapeutically, a dual-drug antithrombotic effect was achieved through the breakdown of fibrin by tenecteplase (TNK) and the inhibition of NET structures by hydroxychloroquine (HCQ). This mechanistically complementary approach showed superior thrombolytic performance in vivo compared to monotherapy, with a residual thrombus rate of 18.7%. Furthermore, the multienzyme-like activities of PBTH NPs restored endothelial function by mitigating oxidative stress damage and inflammation, thereby preventing thrombus recurrence and pulmonary embolism. The vicious cycle of NET-mediated thrombosis-associated immune dysregulation, a locally abnormal thrombotic microenvironment, and endothelial dysfunction was ultimately broken. This work provides a promising two-pronged approach to the treatment of DVT by increasing the effectiveness of thrombolysis while reducing the risk of reocclusion.

Graphical Abstract