Nanoparticles That Sense Thrombin Activity As Synthetic Urinary Biomarkers of Thrombosis
Name
Lin_2013-Nanoparticles that sense.pdf
Size
3.13 MB
Format
Adobe PDF
Checksum (MD5)
c55d76dee3d0c19bd821b46da0bffd23
Author(s)
Kwong, Gabriel A.
Wood, David K.
Lin, Kevin Yu-Ming
Bhatia, Sangeeta N
Warren, Andrew D.
Date Issued
September 2013
Journal
ACS Nano
Publisher
American Chemical Society (ACS)
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
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Whitaker College of Health Sciences and Technology
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
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.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/nn403550c
