Development of cancer cell selective and red absorbing phototheranostic agents

Cancer is still one of the major research areas as it is the second leading cause of death in many countries. Therapeutic features of light are known since the ancient times. The combination of proper light and photosensitizer introduce the photodynamic therapy (PDT), a highly promising treatment modality for cancer and several other diseases. Upon PDT action, photosensitizer (PS) is activated via light of a certain wavelength, and thereby, the generation of a cytotoxic singlet oxygen induce a cell death through necrosis and/or apoptosis. In the scope of PDT, various type of photosensitizers is investigated by altering their photophysical characterization. Cyanine dyes are the most preferable type of photosensitizer due to their remarkable photophysical features. Especially, they have a strong absorption in NIR region (650-1000 nm), in this way, higher penetration depth into the tissues is enabled. A heavy atom decorated and cancer cell selective hemicyanine based PDT agents have become popular in recent years owing to their high singlet oxygen generation capacities as well as minimum side effects. In the first part of this work, a leucine aminopeptidase (LAP) activatable PDT agent (HCL) has been synthesized. HCL is a water soluble, red-shifted, and brominated hemicyanine derivative. In vitro experiments of HCL were performed in A549 (lung) and HCT116 (colon) cancer cells, which have high LAP concentrations. Upon endogenous LAP activation, a remarkable fluorescence enhancement and effective photocytotoxicity were demonstrated. Unlike cancer cells, no fluorescence turn-on and phototoxicity was detected in L929 (healthy) cells. Thus, HCL was shown to be a highly efficient and cancer cell selective PS. It marks the first example of a LAP-sensitive phototheranostic agent. In the second part of the thesis, the effect of heavy atoms located on hemicyanine core was evaluated. Two hemicyanine derivatives HC-1 (brominated) and HC-2 (iodinated) have been synthesized and their singlet oxygen generation efficiencies were compared.