Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents

Junchao Xu, Na Yan, Chunling Wang, Chao Gao, Xuexiang Han, Chengzhi Yang, Jiaqi Xu, Kun Wang, Michael J. Mitchell, Yinlong Zhang, Guangjun Nie

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Background: During long-term antiplatelet agents (APAs) administration, patients with thrombotic diseases take a fairly high risk of life-threatening bleeding, especially when in need of urgent surgery. Rapid functional reversal of APAs remains an issue yet to be efficiently resolved by far due to the lack of any specific reversal agent in the clinic, which greatly restricts the use of APAs. Methods: Flow cytometry analysis was first applied to assess the dose-dependent reversal activity of platelet-mimicking perfluorocarbon-based nanosponges (PLT-PFCs) toward ticagrelor. The tail bleeding time of mice treated with APAs followed by PLT-PFCs was recorded at different time points, along with corresponding pharmacokinetic analysis of ticagrelor and tirofiban. A hemorrhagic transformation model was established in experimental stroke mice with thrombolytic/antiplatelet therapy. Magnetic resonance imaging was subsequently applied to observe hemorrhage and thrombosis in vivo. Further evaluation of the spontaneous clot formation activity of PLT-PFCs was achieved by clot retraction assay in vitro. Results: PLT-PFCs potently reversed the antiplatelet effect of APAs by competitively binding with APAs. PLT-PFCs showed high binding affinity comparable to fresh platelets in vitro with first-line APAs, ticagrelor and tirofiban, and efficiently reversed their function in both tail bleeding and postischemic-reperfusion models. Moreover, the deficiency of platelet intrinsic thrombotic activity diminished the risk of thrombogenesis. Conclusions: This study demonstrated the safety and effectiveness of platelet-mimicking nanosponges in ameliorating the bleeding risk of different APAs, which offers a promising strategy for the management of bleeding complications induced by antiplatelet therapy.

Original languageEnglish (US)
Pages (from-to)339-354
Number of pages16
JournalCirculation Research
Issue number3
StatePublished - Feb 3 2023


  • antiplatelet agents
  • antithrombotic reversal agents
  • bio-inspired engineering
  • hemorrhage
  • platelet transfusion
  • theranostic nanomedicine

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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