title: Targeted drug delivery to flow-obstructed blood vessels using mechanically activated nanotherapeutics.
abstract: Obstruction of normal blood flow, which occurs in a variety of diseases, including thromboembolism in stroke and atherosclerosis, is a leading cause of death and long-term adult disability in the Western world. This review focuses on a novel nanotherapeutic drug-delivery platform that is mechanically activated within blood vessels by high-fluid shear stresses to selectively target drugs to sites of vascular obstruction. In vitro and in vivo studies have shown that this approach can be used to efficiently lyse clots using a significantly lower amount of thrombolytic drug than is required when administered in a soluble formulation. This nanotherapeutic strategy can potentially improve both the efficacy and safety of thrombolytic drugs, particularly in patients who are at high risk for brain hemorrhage, and thus provide a new approach for the treatment of many life-threatening and debilitating vascular disorders.
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts.
authors.forename: Netanel
authors.initials: N
authors.lastname: Korin
authors.affiliation: New England Center for Stroke Research, University of Massachusetts Medical School, Worcester3Department of Radiology, University of Massachusetts Medical School, Worcester.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Gounis
authors.affiliation: New England Center for Stroke Research, University of Massachusetts Medical School, Worcester3Department of Radiology, University of Massachusetts Medical School, Worcester.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Wakhloo
authors.affiliation: Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, Massachusetts4Vascular Biology Program, Children's Hospital and Harvard Medical School, Boston, Massachusetts5School of Engineering and Applied Sciences, Harvard Universit.
authors.forename: Donald E
authors.initials: DE
authors.lastname: Ingber
mesh_terms: D016503:Drug Delivery Systems; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D036103:Nanotechnology / Q000379:methods*; D020521:Stroke / Q000188:drug therapy*
chemical_list: D005343:Fibrinolytic Agents