Journal
SCIENCE ADVANCES
Volume 7, Issue 23, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abf9033
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Funding
- National Institute for Health Research (NIHR) Imperial Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London
- Department of Health and Social Care using UK Aid funding
- Engineering and Physical Sciences Research Council (EPSRC) [EP/R013764/1]
- NIHR University College London Hospitals Biomedical Research Centre
- UK Medical Research Council [MC_UU_12019/1]
- EPSRC [EP/R013764/1] Funding Source: UKRI
- MRC [MC_UU_12019/1] Funding Source: UKRI
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A biomimetic multiarm nanovesicle designed through bioinspired methods can efficiently deliver tPA and target thrombolysis at the site of thrombus with high selectivity and efficacy. Additionally, a novel computational model is capable of simulating thrombolysis process and has potential application in predicting thrombolysis dynamics in physiological scenarios.
Clinical use of tissue plasminogen activator (tPA) in thrombolytic therapy is limited by its short circulation time and hemorrhagic side effects. Inspired by fibrinogen binding to activated platelets, we report a fibrinogen-mimicking, multiarm nanovesicle for thrombus-specific tPA delivery and targeted thrombolysis. This biomimetic system is based on the lipid nanovesicle coated with polyethylene glycol (PEG) terminally conjugated with a cyclic RGD (cRGD) peptide. Our experiments with human blood demonstrated its highly selective binding to activated platelets and efficient tPA release at a thrombus site under both static and physiological flow conditions. Its clot dissolution time in a microfluidic system was comparable to that of free tPA. Furthermore, we report a purpose-built computational model capable of simulating targeted thrombolysis of the tPA-loaded nanovesicle and with a potential in predicting the dynamics of thrombolysis in physiologically realistic scenarios. This combined experimental and computational work presents a promising platform for development of thrombolytic nanomedicines.
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