ArticleJournal of thrombosis and haemostasis : JTH2023
Direct delivery of plasmin using clot-anchoring thrombin-responsive nanoparticles for targeted fibrinolytic therapy.
Article in Journal of thrombosis and haemostasis : JTH, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Transforming stroke care: the promise of feedback-guided thrombolytic nanomedicine.Journal of nanobiotechnology · 2026Review
- Transfusion biomaterials for hemostasis.Journal of thrombosis and haemostasis : JTH · 2025Review
- Injury-on-a-chip for modelling microvascular trauma-induced coagulation.Lab on a chip · 2025Article
- Drug-loaded nanoparticles reduced platelet aggregation and blood coagulation.Frontiers in medical technology · 2025Article
- Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery.Molecules (Basel, Switzerland) · 2024Review
- Sono-responsive smart nanoliposomes for precise and rapid hemostasis application.RSC advances · 2024Article
- pH-Responsive Theranostic Colloidosome Drug Carriers Enable Real-Time Imaging of Targeted Thrombolytic Process with Near-Infrared-II for Deep Venous Thrombosis.Research (Washington, D.C.) · 2024Article
- Multiscale physics-basedFrontiers in drug delivery · 2024Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundFibrin-rich clot formation in thrombo-occlusive pathologies is currently treated by systemic administration of plasminogen activators (e.g. tPA), to convert fibrin-associated plasminogen to plasmin for fibrinolytic action. However, this conversion is not restricted to clot site only but also occurs on circulating plasminogen, causing systemic fibrinogenolysis and bleeding risks. To address this, past research has explored tPA delivery using clot-targeted nanoparticles.
objectivesWe designed a nanomedicine system that can (1) target clots via binding to activated platelets and fibrin, (2) package plasmin instead of tPA as a direct fibrinolytic agent, and (3) release this plasmin triggered by thrombin for clot-localized action.
methodsClot-targeted thrombin-cleavable nanoparticles (CTNPs) were manufactured using self-assembly of peptide-lipid conjugates. Plasmin loading and its thrombin-triggered release from CTNPs were characterized by UV-visible spectroscopy. CTNP-targeting to clots under flow was studied using microfluidics. Fibrinolytic effect of CTNP-delivered plasmin was studied in vitro using BioFlux imaging and D-dimer analysis and in vivo in a zebrafish thrombosis model.
resultsPlasmin-loaded CTNPs significantly bound to clots under shear flow and showed thrombin-triggered enhanced release of plasmin. BioFlux studies confirmed that thrombin-triggered plasmin released from CTNPs rendered fibrinolysis similar to free plasmin, further corroborated by D-dimer analysis. In the zebrafish model, CTNP-delivered plasmin accelerated time-to-recanalization, or completely prevented occlusion when infused before thrombus formation.
conclusionConsidering that the very short circulation half-life (<1 second) of plasmin prevents its systemic use but also makes it safer without off-target drug effects, clot-targeted delivery of plasmin using CTNPs can enable safer and more efficacious fibrinolytic therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.