Nanomedicine for the targeted treatment of venous thromboembolism

Venous thromboembolism (VTE) is an entity that includes deep vein thrombosis (DVT) and pulmonary embolism (PE), unresolved PE may leave chronic thromboembolic pulmonary hypertension (CTEPH). Administration of fibrinolytic agents is necessary in some cases of VTE despite the high risk of hemorrhagic complications. A nanomedicine has been designed and developed for the treatment of VTE. Cysteine–arginine–glutamic acid–lysine–alanine clot-binding peptide (CREKA) was conjugated to nanoparticles to release two drugs: tissue-type plasminogen activator (tPA) and recombinant human DNase. <bold>Objectives:</bold> to evaluate the effects of nanoparticles in a model of vena cava thrombosis in C57BL6/J mice by i.v. administration. Thrombus volumes were obtained on magnetic resonance imaging at different follow-up stages. We show the results of different nanoparticles according to the drugs administered (A), follow-up thrombosis volume when treated with DNAse 40.000U/kg +TPA 10mg/kg targeting thrombus with CREKA nanoparticles (B) and a generalised linear mixed model (C) of DNAse 40.000U/kg +TPA 10mg/kg targeting thrombus with CREKA nanoparticles and usual fibrinolytic treatment (TPA 10mg/kg). <bold>Conclusions:</bold> Combined thrombus-targeted by CREKA nanoparticles delivering DNAsa 40.000U/kg +TPA 10mg/kg may be slightly better at reducing thrombus than usual fibrinolytic therapy and potentially safer. Funding: Junta de Andalucía (PROYEXCEL_00691) and FSE 2014-2020 (RH-0116-2020). <fig><object-id>erj;64/suppl_68/OA5549/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>