Nanomaterials for the detection of cancer-associated biomarkers

Prostate cancer persists as a major public health issue in the United States and remains the second leading cause of cancer death in men. Early detection and disease monitoring in prostate cancer can significantly improve a patient's prognosis. The advent of prostate-specific antigen (PSA) screening has allowed physicians to monitor the levels of a specific protein, or biomarker, as a correlate of disease progression. This thesis focuses on optical detection of prostate tumors through the development of biomarker-targeted molecular imaging probes. In the first part of this work, engineered human prostate cancer cell lines were developed and characterized to determine the dynamics of post-translational processing for PSA proteolytic activity and to establish potential small animal models for validating protease-activatable imaging probes. Target-activatable gold nanoparticle imaging probes that can be self-assembled in a one-step reaction were then developed to detect biomarker proteases in vivo. The activated probes demonstrated a 5 to 8-fold fluorescence signal amplification, extended circulation time, and high image contrast in a mouse tumor model. Lastly, differential phage display selection was performed on human prostate cancer cells with low and high metastatic potentials to (1) identify cell-surface biomarkers specific to highly aggressive tumors, and (2) develop molecular imaging probes for detecting prostate cancer metastases.

Department dc:contributor.department

Harvard University--MIT Division of Health Sciences and Technology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2010

Author dc:creator

• Mu, Chunyao Jenny

Advisor dc:contributor.advisor

• Bruce R. Zetter and Robert S. Langer.

• Harvard University--MIT Division of Health Sciences and Technology.

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/1721.1/57782

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/57782