Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels
- PMID: 22767894
- DOI: 10.1126/science.1217815
Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels
Erratum in
- Science. 2012 Sep 21;337(6101):1453
Abstract
Obstruction of critical blood vessels due to thrombosis or embolism is a leading cause of death worldwide. Here, we describe a biomimetic strategy that uses high shear stress caused by vascular narrowing as a targeting mechanism--in the same way platelets do--to deliver drugs to obstructed blood vessels. Microscale aggregates of nanoparticles were fabricated to break up into nanoscale components when exposed to abnormally high fluid shear stress. When coated with tissue plasminogen activator and administered intravenously in mice, these shear-activated nanotherapeutics induce rapid clot dissolution in a mesenteric injury model, restore normal flow dynamics, and increase survival in an otherwise fatal mouse pulmonary embolism model. This biophysical strategy for drug targeting, which lowers required doses and minimizes side effects while maximizing drug efficacy, offers a potential new approach for treatment of life-threatening diseases that result from acute vascular occlusion.
Comment in
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Medicine. Leveraging shear stress to bust clots with nanoparticles.Science. 2012 Aug 10;337(6095):658-9. doi: 10.1126/science.1227097. Science. 2012. PMID: 22879494 No abstract available.
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Ischaemic disorders: Nanotherapeutic delivers clot-busting drug.Nat Rev Drug Discov. 2012 Sep;11(9):672. doi: 10.1038/nrd3828. Epub 2012 Aug 20. Nat Rev Drug Discov. 2012. PMID: 22903044 No abstract available.
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Shear-activated nanotherapeutics.Nanomedicine (Lond). 2012 Nov;7(11):1653. doi: 10.2217/nnm.12.148. Nanomedicine (Lond). 2012. PMID: 23210713 No abstract available.
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