Executive Summary : | The study aims to use nitroreductase (NTR) as a biomarker to monitor hypoxia in tumor cells under hypoxic conditions. Nitroaromatic compounds, which possess high stability under physiological conditions, are used as substrates for NTR in hypoxic cells. The researchers propose constructing a device using these complexes as markers to probe hypoxia. The hypothesis is to determine if the quantitation of NTR can be directly correlated to tumor detection using metal-based fluorogenic probes. The main experiments will involve synthesizing proposed ligands, determining their identities through NMR and HRMs, and characterization of corresponding Cu(II) and Fe(III) complexes. Fluorescence changes after treatment with increasing concentration of NTR and fixed NADH concentration will be monitored, and the percentage of hypoxia will be calculated. Cancer cells will be grown under controlled oxygen conditions and imaged, while the accumulation of compounds in solid tumors will be studied. Cytotoxicity profiles will be tested, and a serological test for hypoxia quantitation will be developed based on NTR activity. The study's significance lies in the need for low-cost point-of-care diagnostics for early detection of diseases, such as cancer, which can save lives and money. The researchers propose using NTR as a biomarker to develop a diagnostic tool using metal-based fluorogenic probes designed in their laboratory. |