Nanoparticle-chaperoned urinary 'synthetic biomarkers' for profiling proteases in cancer

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.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Mechanical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2012

Author dc:creator

• Abudayyeh, Omar O

Advisor dc:contributor.advisor

• Sangeeta Bhatia and Scott Manalis.

• Mechanical Engineering.

Statement dc:rights

• 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.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/74430

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/74430