dc.contributor.author | Kwong, Gabriel A. | |
dc.contributor.author | Wood, David K. | |
dc.contributor.author | Lin, Kevin Yu-Ming | |
dc.contributor.author | Bhatia, Sangeeta N | |
dc.contributor.author | Warren, Andrew D. | |
dc.date.accessioned | 2013-11-12T17:46:19Z | |
dc.date.available | 2013-11-12T17:46:19Z | |
dc.date.issued | 2013-09 | |
dc.date.submitted | 2013-07 | |
dc.identifier.issn | 1936-0851 | |
dc.identifier.issn | 1936-086X | |
dc.identifier.uri | http://hdl.handle.net/1721.1/82092 | |
dc.description.abstract | Thrombin is a serine protease and regulator of hemostasis that plays a critical role in the formation of obstructive blood clots, or thrombosis, that is a life-threatening condition associated with numerous diseases such as atherosclerosis and stroke. To detect thrombi in living animals, we design and conjugate thrombin-sensitive peptide substrates to the surface of nanoparticles. Following intravenous infusion, these “synthetic biomarkers” survey the host vasculature for coagulation and, in response to substrate cleavage by thrombin, release ligand-encoded reporters into the host urine. To detect the urinary reporters, we develop a companion 96-well immunoassay that utilizes antibodies to bind specifically to the ligands, thus capturing the reporters for quantification. Using a thromboplastin-induced mouse model of pulmonary embolism, we show that urinary biomarker levels differentiate between healthy and thrombotic states and correlate closely with the aggregate burden of clots formed in the lungs. Our results demonstrate that synthetic biomarkers can be engineered to sense vascular diseases remotely from the urine and may allow applications in point-of-care diagnostics. | en_US |
dc.description.sponsorship | Kathy and Curt Marble Cancer Research Fund | en_US |
dc.description.sponsorship | Koch Institute Frontier Research Program | en_US |
dc.description.sponsorship | Mazumdar-Shaw International Oncology Fellows Program | en_US |
dc.description.sponsorship | Deshpande Center for Technological Innovation | en_US |
dc.description.sponsorship | CCNE (5 U54 CA151884-03) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (F32CA159496-02)) | en_US |
dc.description.sponsorship | Burroughs Wellcome Fund (Career Award at the Scientific Interface) | en_US |
dc.language.iso | en_US | |
dc.publisher | American Chemical Society (ACS) | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1021/nn403550c | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | PMC | en_US |
dc.title | Nanoparticles That Sense Thrombin Activity As Synthetic Urinary Biomarkers of Thrombosis | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Lin, Kevin Y., Gabriel A. Kwong, Andrew D. Warren, David K. Wood, and Sangeeta N. Bhatia. “Nanoparticles That Sense Thrombin Activity As Synthetic Urinary Biomarkers of Thrombosis.” ACS Nano 7, no. 10 (October 22, 2013): 9001-9009. © 2013 American Chemical Society | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Institute for Medical Engineering & Science | en_US |
dc.contributor.department | Whitaker College of Health Sciences and Technology | en_US |
dc.contributor.department | Harvard University--MIT Division of Health Sciences and Technology | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Lin, Kevin Yu-Ming | en_US |
dc.contributor.mitauthor | Kwong, Gabriel A. | en_US |
dc.contributor.mitauthor | Warren, Andrew David | en_US |
dc.contributor.mitauthor | Wood, David K. | en_US |
dc.contributor.mitauthor | Bhatia, Sangeeta N. | en_US |
dc.relation.journal | ACS Nano | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Lin, Kevin Y.; Kwong, Gabriel A.; Warren, Andrew D.; Wood, David K.; Bhatia, Sangeeta N. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-1293-2097 | |
dc.identifier.orcid | https://orcid.org/0000-0003-1948-0289 | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |