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Theranostic Curcumin Rare-Earth Agents

The theranostic approach is the combination of therapy and diagnosis and can be viewed as a possible tool helping the transformation of conventional, non-specific medicine towards contemporary precision or personalized medicine. Bioimaging and biosensing are emerging areas to gain in-depth insights into cellular functions and provide a wide range of diagnostic parameters in accurate diagnosis, as well as treatment of diseases. Metal-based optical probes can be utilized for imaging cancer cells by fluorescence microscopy to study the cellular localization of the metal complexes besides damaging the cancer cells on photo-irradiation. Being curcumin a molecule with an UV-visible absorption band in the 350–500 nm region and a fluorophore with green emission property, it can be a promising antenna for the sensitization of the luminescence of selected metal ions. In fact, among optical sensors, transition and lanthanide metal complexes have attracted recent attention as alternatives to conventional dyes due to their advantages of large Stokes shifts, long lifetimes, and ease of structural modifications. The aim of this project is to develop NIR-to-NIR probes by interacting selected Ln(III) acceptors with a library of curcuminoid ligands to afford metal complexes with the ability to give non-linear optical (NLO) phenomenon, such as the Two-Photon (2P) absorption, acting as optical probes in cancer diseases. Next, we will screen in silico (molecular docking) and in vitro (biosensor-based analyses) these compounds based on their affinity and specificity for a selection of prognostic biomarkers of hepatocellular carcinoma (the most frequent form of primary liver cancer), to identify a subset of optimal probes to be used for cellular imaging by fluorescence microscopy with the aim of differentiating between HepG2 cancer cells and normal cells. Moreover, we aim to investigate these metal complexes as potential theranostic agents for hepatic cancer in Photo Dynamic Therapy (PDT) upon their excitation by irradiation under Near-InfraRed (NIR) light, which is less dangerous for cells than UV light and it has higher depth of penetration in tissues. Induction of apoptotic events along with the molecular mechanisms underlying cell response to this photoinduced treatment will be explored by monitoring a set of parameters including cell proliferation, morphological appearance, involvement of nucleases or proteases, DNA damage and mitochondrial functionality. Results from these studies will provide an innovative strategy to generate anticancer molecules able to identify and simultaneously/selectively kill cancer cells.

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