Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels. Science 2012 Aug 10;337(6095):738-42
Date
07/07/2012Pubmed ID
22767894DOI
10.1126/science.1217815Scopus ID
2-s2.0-84864832183 (requires institutional sign-in at Scopus site) 421 CitationsAbstract
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.
Author List
Korin N, Kanapathipillai M, Matthews BD, Crescente M, Brill A, Mammoto T, Ghosh K, Jurek S, Bencherif SA, Bhatta D, Coskun AU, Feldman CL, Wagner DD, Ingber DEAuthor
Tadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBiomimetic Materials
Blood Circulation
Drug Delivery Systems
Fibrinolytic Agents
Hemodynamics
Hemorheology
Lactic Acid
Male
Mesenteric Arteries
Mesenteric Vascular Occlusion
Mice
Mice, Inbred C57BL
Microfluidic Analytical Techniques
Models, Anatomic
Nanoparticles
Polyglycolic Acid
Pulmonary Embolism
Stress, Mechanical
Thrombosis
Tissue Plasminogen Activator