Malignant melanoma is the most rapidly increasing cancer throughout the world. Current methods for detection of metastatic melanoma are not adequate. At least 20% of patients develop advanced disease, which is rarely curable. In this application, we propose a training program for an electrical engineer who is an expert in nanotechnology so that he can better understand the clinical needs for early detection of cancer, especially melanoma. This training experience will establish the applicant as a truly interdisciplinary expert well versed in both cancer biology and nanotechnology. It will also establish a lasting collaboration between the applicant and the sponsors that will explore the new frontiers of cancer nanotechnology. The training will have two phases: (1) understanding and identifying DNA and RNA biomarkers for melanoma and (2) developing nanotechnology platform for detection and manipulation of the biomarkers. The biomarkers to be investigated include BRAF mutations, melanocortin 1 receptor mutations, and microRNA expression. We will study the expression levels and their effects in melanoma cells and normal melanocytes. A particular emphasis will be placed on understanding their effects in conjunction with the nanoprobes to be developed concurrently. The nanoscale probes will be optimized for rapid, high-specificity detection of melanoma cells at extremely low concentrations. Specifically, we will investigate new synthesis and conjugation techniques for nanoprobes which will include noble metal nanoparticles, nanorods and nanoshells. Using these probes, we will investigate two technology platforms: (1) fluidic-based technique in which nanoprobes are suspended and interact with other biomolecules in solution (e.g., blood sample); and (2) optical imaging and targeting by nanoprobe injection into melanoma cells. For (1), we will develop a highly integrated nano- and micro-fluidic system in which a microscopic amount of sample is accurately manipulated and examined for high-sensitivity detection and imaging. For (2), we will investigate in detail the intake process of nanoprobes by various cells and the dynamics and interaction of nanoprobes inside the cell.

RELEVANCE TO PUBLIC HEALTH: Malignant melanoma is the most rapidly increasing cancer throughout the world and at least 20% of melanoma patients develop advanced disease which is rarely curable. Methods for early detection is therefore a high priority and new strategies for effective treatment and management of the disease are highly desired. The proposed training program seeks to apply nanotechnology to the detection and treatment of melanoma cells.

F33CA136151

2008-09-09

2009-09-08