Nanotechnology enabled targeting of p53 deficiency in human cancer

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Project Summary/Abstract Cancer is a major global health problem and is the second leading cause of death in the United States. The early detection of cancer is vital to help stop the spread of cancer. Circulating tumor cells (CTCs) are a hallmark of this invasive behavior of cancer. These cells detach from the primary tumor, break down the basement membrane of blood vessels, and migrate into the blood or lymphatic circulation. They translocate to distant tissues where they adapt to the new microenvironment, and eventually seed and colonize to form metastases. Current cancer detection techniques are not sensitive enough to be able to detect cancer at its earliest stage. However, existing treatments could be effective only when cancer has not metastasized yet. Therefore, being able to detect cancer early before metastasis increases survival rates. Recent studies have found that CTCs carry information about the primary tumor and have the potential to be valuable biomarkers for cancer diagnosis and progression. They also allow molecular characterization of certain biological properties of the primary tumor. Molecular characterization of CTCs has proven to have a great potential to assess the phenotypic and genotypic features of a cancer without the need for invasive biopsy of the primary tumor. This allows for minimally invasive patient monitoring and response assessment of cancer treatment. However, CTC detection is hindered by its low concentration in blood and contemporary techniques for CTC detection have had several major drawbacks such as low repeatability, sensitivity, and specificity. The goal of this supplemental application is to create an effective approach to capture CTCs from blood samples of cancer patients with high repeatability, sensitivity, and specificity for early cancer detection. This will be achieved by fabricating a gold-coated electro-micro-fluidic device with distinct capture and flow zones in the main channel (AuZonesChip) and using patterned dielectrophoretic force to direct cells from the flow zone into the capture zone. This separation of the capture and flow zones minimizes the negative impact of high flow speed. The polydimethylsiloxane (PDMS) electro-micro-fluidic device will be coated with a 15 nm thick gold layer and surface modified with thiolated capturing antibody. Thiolated capturing antibodies will be flown through the gold-coated electro-micro-fluidic device, to modify the surface of the main channel with the capturing antibody by utilizing the high affinity between gold and the thiol group. The surface antigens on CTCs from patient blood will allow them to be captured by antibodies modified on the surface of the device due to the high antigen- antibody binding affinity. Another important goal of this supplement application is to promote diversity in health- related research. This will be achieved by training postdoc from a minority group, who will be exemplary to encourage more minority groups to participate in biomedical science research.