Early detection of cancer is essential to improve patient's survival rates and quality of life. Near-infrared (NIR) optical imaging using a NIR fluorescent contrast agent is one relatively undeveloped modality for tumor detection whose potential has not yet been fully realized. Lanthanide ions (Ln3+) have luminescent properties well suited for application as NIR contrast agents and one promising platform for sensitization of Ln3+ ions for NIR fluorescence is a class of supramolecular structures called metallacrowns (MC). The focus of this proposal will be to synthesize and develop Ln3+[MC] complexes for tumor imaging applications. Specifically we will 1) synthesize a series of Ln3+[MC] structures and characterize their photophysical properties in order to determine the energy transfer mechanism, 2) design new MC ligands to absorb in the visible region while attaching peptide translocation vectors, and 3) assess in vitro biocompatibility against a range of tumor cell lines. Using the series of Ln3+[MC] structures that have been synthesized to date, key photophysical parameters, such as emission wavelength (?f), fluorescence quantum yield (?f), fluorescence lifetime (?f), and hydration number (q), will be tabulated providing the necessary information for further synthetic refinement and optimization of NIR fluorescence. Deuterated ligands will be explored to determine which parts of the molecule participate in energy transfer to the Ln3+ ion. New ligands based on fluorone dyes will also be made to further shift the absorption into the visible. These new ligands will allow introduction of functional groups for conjugation to tumor targeting peptides which will be synthesized de novo. Finally, Ln3+[MC]s with the most promising optical properties and those conjugated to tumor targeting peptides will be advanced to in vitro studies of biocompatibility that will include examination of solution stability, cell viability, celular uptake, and intracellular fluorescence. Overall, this synthetic strategy followed by preliminary biological assessment will inform further synthetic refinement. Completion of these studies will provide a better understanding of the fluorescent properties of Ln3+[MC]s and identify promising candidates for practical application as NIR fluorescent tumor contrast agents.
Early stage cancer detection greatly improves patient survival rates. Fluorescent contrast agents that accumulate in tumors have the potential to aid in early cancer diagnosis by causing tumors to light up or glow. We will synthesize, optically characterize, and test the biocompatibility of a new class of near IR fluorescent contrast agents, the lanthanide metallacrowns, for application as probes for early tumor detection.
| Sgarlata, Carmelo; Giuffrida, Alessandro; Trivedi, Evan R et al. (2017) Anion Encapsulation Drives the Formation of Dimeric GdIII[15-metallacrown-5]3+ Complexes in Aqueous Solution. Inorg Chem 56:4771-4774 |
| Trivedi, Evan R; Eliseeva, Svetlana V; Jankolovits, Joseph et al. (2014) Highly emitting near-infrared lanthanide ""encapsulated sandwich"" metallacrown complexes with excitation shifted toward lower energy. J Am Chem Soc 136:1526-34 |
