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Peer-reviewedCC BY-NC-NDBioactive materials

Biomimetic sequential targeted nanoplatform for synergistic thrombolysis in ischemic stroke.

  • Jingwen Wang1
  • Xinxin Wang1
  • Saiya Liu1
  • Yan Zheng1
  • Chunhao Wang1
  • Jianjun Cheng2
  • Xu Wang1
  1. 1Tianjin Key Laboratory of Technologies Enabling Development on Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
  2. 2Department of Materials Science and Engineering, Westlake University, Hangzhou, Zhejiang, 310030, China.
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Abstract

Conventional thrombolytic drugs for vascular blockage such as tissue plasminogen activator (tPA) are challenged by the low bioavailability, off-target side effects and limited penetration in thrombi, leading to delayed recanalization. Herein, we developed a sequential targeted nanoplatform for efficient thrombolysis based on the thrombolysis-neuroprotection integrated strategy. The mesoporous silica layer-modified upconversion nanoparticle (UCNP) was loaded with the nitric oxide (NO) donors (BNN6), further coating platelet membranes (PMs) on the surface of UCNP. tPA was conjugated onto PMs using the MMP9-responsive peptide as a linker to form a multifunctional drug carrier of UCNP/BNN6@PM-tPA. The proposed drug carrier maintained stability in the blood circulation to reduce bleeding risk (protection), facilitating it colonizing at the thrombus clots. MMP-9 triggered the release of tPA to realize rapid thrombolysis (attack), whereas continuous NO release from NIR-irradiated BNN6 acted to prevent vascular re-embolization (defense). In vitro and in vivo evaluation revealed that UCNP/BNN6@PM-tPA enables thrombus-homing accumulation, fluorescence imaging-guided thrombolysis, and NO mediated prevention of thrombosis recurrence, displaying favorable therapeutic outcomes with low bleeding risk. This study offers a facile, safe, and effective way towards the clinical treatment of thrombosis and ischemic stroke.

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Cite

BibTeXRIS
BibTeX
@article{wang2026biomimetic,
  title = {{Biomimetic sequential targeted nanoplatform for synergistic thrombolysis in ischemic stroke.}},
  author = {Jingwen Wang and Xinxin Wang and Saiya Liu and Yan Zheng and Chunhao Wang and Jianjun Cheng and Xu Wang},
  journal = {Bioactive materials},
  year = {2026},
  month = oct,
  doi = {10.1016/j.bioactmat.2026.10.014},
  url = {https://europepmc.org/article/MED/42909374},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Biomimetic sequential targeted nanoplatform for synergistic thrombolysis in ischemic stroke.
AU  - Jingwen Wang
AU  - Xinxin Wang
AU  - Saiya Liu
AU  - Yan Zheng
AU  - Chunhao Wang
AU  - Jianjun Cheng
AU  - Xu Wang
PY  - 2026
DA  - 2026/10/13
JO  - Bioactive materials
DO  - 10.1016/j.bioactmat.2026.10.014
UR  - https://europepmc.org/article/MED/42909374
AB  - Conventional thrombolytic drugs for vascular blockage such as tissue plasminogen activator (tPA) are challenged by the low bioavailability, off-target side effects and limited penetration in thrombi, leading to delayed recanalization. Herein, we developed a sequential targeted nanoplatform for efficient thrombolysis based on the thrombolysis-neuroprotection integrated strategy. The mesoporous silica layer-modified upconversion nanoparticle (UCNP) was loaded with the nitric oxide (NO) donors (BNN6), further coating platelet membranes (PMs) on the surface of UCNP. tPA was conjugated onto PMs using the MMP9-responsive peptide as a linker to form a multifunctional drug carrier of UCNP/BNN6@PM-tPA. The proposed drug carrier maintained stability in the blood circulation to reduce bleeding risk (protection), facilitating it colonizing at the thrombus clots. MMP-9 triggered the release of tPA to realize rapid thrombolysis (attack), whereas continuous NO release from NIR-irradiated BNN6 acted to prevent vascular re-embolization (defense). In vitro and in vivo evaluation revealed that UCNP/BNN6@PM-tPA enables thrombus-homing accumulation, fluorescence imaging-guided thrombolysis, and NO mediated prevention of thrombosis recurrence, displaying favorable therapeutic outcomes with low bleeding risk. This study offers a facile, safe, and effective way towards the clinical treatment of thrombosis and ischemic stroke.
SN  - 2452-199X
ER  -