Webinar recording : BioFlux, the gold standard for Platelet Biology and Thrombosis research

The BioFlux system give you the ability to introduce physiological shear flow to your research and drug discovery experiments, effectively emulating in vivo conditions for Platelet Biology and Vascular Pharmacology studies.

Thrombosis, the underlying cause of major fatal conditions like ischemic stroke and myocardial infarction, poses a challenge for treatment. Tissue plasminogen activator (tPA), the primary nonsurgical remedy, faces limitations due to high hemorrhagic risk and a low success rate in clearing thrombi. Neutrophil extracellular traps (NETs), protein-rich structures in blood clots, contribute to tPA resistance. In our microfluidic models of NET-rich clots, we discovered a core-shell structure, with the shell showing significant tPA resistance. The incorporation of DNAse, an enzyme degrading NETs, restored clot tPA susceptibility. Based on these findings, we proposed a localized co-delivery strategy using a liposomal drug delivery platform. Two types of nanoparticles were engineered: tPA-loaded nanoparticles (tPA-NP) and DNAse-loaded nanoparticles (DNAse-NP). Thrombin and neutrophil elastase-cleavable substrates ensured controlled release upon exposure to clot-specific enzymes. tPA-NP demonstrated fibrinolytic potential comparable to solvated tPA, while DNAse-NP exhibited NET-lytic activity. Alone, neither fully addressed clot lysis in functional assays. However, the combined delivery of DNAse-NP and tPA-NP achieved complete clot dissolution within 12 minutes. This approach presents a tunable, modular, and efficacious drug delivery platform for overcoming thrombosis resistant to traditional therapies.

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