2026-09-18T19:46:51Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/744302022-01-13T07:54:36Zcom_1721.1_7582com_1721.1_7581col_1721.1_131024
Sangeeta Bhatia and Scott Manalis.
Abudayyeh, Omar O
Massachusetts Institute of Technology. Dept. of Mechanical Engineering.
Massachusetts Institute of Technology. Department of Mechanical Engineering
2012-10-26T18:08:24Z
2012-10-26T18:08:24Z
2012
2012
http://hdl.handle.net/1721.1/74430
813051294
Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2012.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 61-63).
Many biomarker-based diagnostics have poor predictive value because of their dependence on naturally occurring endogenous biomolecules to indicate disease. This work presents a diagnostic platform that uses nanoparticles to profile underlying proteolytic signatures of diseases. In this thesis, work is presented on long circulating peptide-nanoparticle probes that can survey, sense, and remotely report on dysregulated protease activities in cancer. In this strategy, iron oxide nanoparticles are utilized as chaperons to deliver protease-specific peptide libraries to tumors whereupon selective cleavage by active proteases releases peptide fragments that are cleared by the renal system into the urine. These peptide fragments are pre-designed with internal photolabile triggers that un-cage isobaric peptide mass tags optimized for multiplexed LC MS/MS quantification. Results demonstrate that such peptide 'synthetic biomarker' panels uncover unique proteolytic signatures that can be correlated with disease states, allowing for the detection of cancer and potential long-term monitoring of disease using an implantable form. This concept of administering prodiagnostic reagents and analyzing remote reporters is amenable to a broad range of protease-dependent complex diseases, such as liver fibrosis and coagulopathies, and infectious disease.
by Omar O. Abudayyeh.
S.B.
63 p.
eng
Massachusetts Institute of Technology
M.I.T. theses are protected by
copyright. They may be viewed from this source for any purpose, but
reproduction or distribution in any format is prohibited without written
permission. See provided URL for inquiries about permission.
http://dspace.mit.edu/handle/1721.1/7582
Mechanical Engineering.
Nanoparticle-chaperoned urinary 'synthetic biomarkers' for profiling proteases in cancer
Thesis
application/pdf
false
Publication
unknown
unknown
<Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="4fd68702-6eea-4995-871e-cb11bcf55584">
<Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type>
<Language>eng</Language>
<Title>Nanoparticle-chaperoned urinary 'synthetic biomarkers' for profiling proteases in cancer</Title>
<PublishedIn>
<Publication>
</Publication>
</PublishedIn>
<PublicationDate>2012</PublicationDate>
<Authors>
<Author>
<DisplayName>Abudayyeh, Omar O</DisplayName>
<Affiliation>
<OrgUnit>
</OrgUnit>
</Affiliation>
</Author>
</Authors>
<Editors>
</Editors>
<Publishers>
<Publisher>
<DisplayName>Massachusetts Institute of Technology</DisplayName>
<OrgUnit />
</Publisher>
</Publishers>
<License>http://dspace.mit.edu/handle/1721.1/7582</License>
<Keyword>Mechanical Engineering.</Keyword>
<Abstract>Many biomarker-based diagnostics have poor predictive value because of their dependence on naturally occurring endogenous biomolecules to indicate disease. This work presents a diagnostic platform that uses nanoparticles to profile underlying proteolytic signatures of diseases. In this thesis, work is presented on long circulating peptide-nanoparticle probes that can survey, sense, and remotely report on dysregulated protease activities in cancer. In this strategy, iron oxide nanoparticles are utilized as chaperons to deliver protease-specific peptide libraries to tumors whereupon selective cleavage by active proteases releases peptide fragments that are cleared by the renal system into the urine. These peptide fragments are pre-designed with internal photolabile triggers that un-cage isobaric peptide mass tags optimized for multiplexed LC MS/MS quantification. Results demonstrate that such peptide 'synthetic biomarker' panels uncover unique proteolytic signatures that can be correlated with disease states, allowing for the detection of cancer and potential long-term monitoring of disease using an implantable form. This concept of administering prodiagnostic reagents and analyzing remote reporters is amenable to a broad range of protease-dependent complex diseases, such as liver fibrosis and coagulopathies, and infectious disease.</Abstract>
<Access xmlns="http://purl.org/coar/access_right"
>
</Access>
</Publication>