This proposal describes a research program in the development of novel diagnostic cancer imaging and sensing techniques for real-time cancer related protein monitoring using molecular beacon aptamers. Up to now, there are limited diagnosis techniques to probe and to understand the process involved in the initiation and growth of cancer, which greatly hinders our ability in early diagnosis of cancer and the effective treatment of cancer patients. The development of innovative ultrasensitive imaging and sensing methods at the cellular and molecular levels is urgently needed, with a particular emphasis on identification and characterization of either the early formation of cancer or early molecular changes during intervention or therapy. It is thus this proposal's goal to develop imaging and sensing techniques for cancer diagnosis, especially early diagnosis on the cellular and molecular level. Specifically, we aim at developing effective imaging and sensing techniques for in vivo recognition and monitoring of oncoproteins, which are important cancer biomarkers. The proposed research will capitalize upon our recent advancements in developing aptamers and molecular beacons for protein detection, in nanotechnology for ultrasmall biochemical sensors and imaging techniques, in optical imaging at the single molecule level and in single living cell studies. Specifically, we will pursue the following aims in this R21 exploratory proposal: 1) Develop a novel fluorescent molecular probe for cancer protein recognition by combining the specificity of aptamers and the signal transduction mechanism in molecular beacons; 2) Develop ultrasensitive optical fiber biosensors and advanced imaging and biosensing techniques based on the newly developed molecular beacon aptamer; 3) Explore the feasibility of using the molecular beacon aptamer as a diagnostic cancer probe. We will take the following three steps to test the feasibility in this proposal. We will first identify an existing aptamer designed for an oncoprotein, platelet-derived growth factor (PDGF), related to cancer. We will then combine molecular beacon's signal transduction mechanism with the aptamer's binding specificity for the development of a molecular beacon aptamer for the PDGF detection. Once the molecular beacon aptamer is developed, we will combine our existing imaging and biosensing technology with it for ultrasensitive detection of oncoprotein. The new imaging and sensing techniques will then be applied for tumor cell line and tissue sample study. By the completion of this study, we will have developed efficient molecular beacon aptamers as novel protein probes for tumor visualization. We will have developed novel imaging and biosensing technologies based on the new aptamer. for cancer diagnosis at the cellular and molecular levels. These technological innovations can be applied to greatly improve our ability in detecting cancer at its early stages, in cancer growth studies on the molecular and cellular levels, and in understanding of the physiological states of organ and tumor systems. We fully anticipate the results of this study will be widely useful in the development of novel approaches to the treatment of cancer and related disorders.
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