Novel Luminescent Inorganic and Organometallic Transition Metal Glucose and Fructose Complexes and Their Applications as Cellular Probes for Sugar Uptake, Bioimaging Reagents, and Metabolic Indicators
DescriptionThis project aims to develop luminescent inorganic and organometallic transition metal glucose and fructose complexes as a new generation of cellular probes for sugar uptake, bioimaging reagents, and metabolic indicators. Due to the hydrophilic nature of glucose, it is transported through the plasma membranes via facilitative glucose transporters (GLUTs). As extra energy is required for uncontrolled cell proliferation, most cancer cells overexpress GLUTs and show enhanced glucose uptake and metabolism. The substrates of these transporters are not limited to glucose but also include other hexoses such as fructose. Thus, a number of glucose and fructose derivatives have been developed as sugar uptake indicators and imaging reagents for cancer cells. Although radionuclides have been commonly used in imaging cancer cells, optical methods have emerged as an alternative as they offer excellent spatial and temporal resolution. Also, fluorescent reagents allow uptake in individual cells to be monitored and enable simultaneous bioimaging and measurements of other intracellular parameters. As cell metabolism is closely related to the expression of GLUTs and glucose uptake, fluorescent sugar reagents can provide an effective screening method to study the metabolic rates and viability of cells.Although many fluorescent sugar derivatives have been developed, the use of luminescent transition metal glucose and fructose complexes in sugar uptake and bioimaging is relatively unexplored. We anticipate that luminescent inorganic and organometallic transition metal glucose and fructose complexes will be attractive choices as new cellular probes for sugar uptake and bioimaging reagents due to their environment-sensitive emission properties, high photostability, and long emission lifetimes. The use of transition metal complexes means that cellular uptake can be conveniently measured by ICP-MS. Also, strategies to control the cellular uptake efficiency and cytotoxicity of these complexes have been developed. In this project, we will design new luminescent inorganic and organometallic transition metal glucose and fructose complexes, and study their photophysical, photochemical, and electrochemical properties and lipophilicity. The cytotoxicity, cellular uptake, and bioimaging properties of the probes will also be examined using various cell lines. Emphasis will be placed on understanding the possible interactions of these complexes with GLUTs and their selective uptake by cancer cells. Ultimately, the potential use of these complexes as cellular probes for sugar uptake, bioimaging reagents, and metabolic indicators will be examined.
|Effective start/end date||1/09/12 → 1/08/16|