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Luminescent Lanthanide Dendrimer Complexes as Markers for Tumor Detection in Vivo
Luminescence is an attractive strategy for the detection of cancer tumor due to its high sensitivity and the versatility of the instrumentation that allow low cost detection and easy location of the detection systems to the experiment or to the patient. The actual bottleneck is related to the reagents that would allow sensitive and selective detection in real-time in living biological systems. Luminescence based on lanthanide cations offer several advantages over organic fluorophores and semi-conductors including sharp emission bands that allow for spectral discrimination from autofluorescence and multiplex detection, emission in the near-infrared, long luminescence lifetime for temporal discrimination and strong resistance to photobleaching. The main idea of this proposal is to create and use new lanthanide-based luminescent markers for in vivo tumor detection. These compounds will be used for in vivo imaging at the cellular (microscopy) and small animals (macroscopy) levels. The proposed work includes design of visible and near-infrared emitting dendrimers, detailed investigation of their spectroscopic properties, as well as in vivo tests on cells and small animals by microscopy and macroscopy to evaluate the potential of these systems for practical applications. Proposed unique dendrimer technology is a versatile tool allowing (1) the enhancement of detection sensitivity since many lanthanide ions and lanthanide sensitizers can be combined within one discrete molecule (increase of the density of photons), (2) the attachment of a broad variety of lanthanide sensitizers, including those allowing low energy excitation (in the visible range) that are less harmful for biological systems, and (3) the conjugation with a large variety of peptides for selective tumor targeting. Overall, as a result of this project, we will be able to deliver a family of luminescent lanthanide markers for tumor imaging that will allow for enhanced detection sensitivity, improved tumor detection selectivity and versatility of the targeted type of tumor.