Click chemistry mediated cell uptake – towards triggered Auger therapy

Abstract

Many radionuclides used for diagnostic purposes (e.g. 99mTc, 111In) emit Auger electrons besides gamma radiation. These low-energy electrons possess limited range in tissue, and are thus unlikely to cause radiation induced cytotoxicity. However, when the location of decay is within the cell nucleus, Auger electrons cause DNA strand breaks and thus induce cell death. Within this thesis, steps towards the triggered relocation into nucleus are taken. For this purpose, a tumor targeting agent (TTA) is modified with a click tag and a fluorescent dye. The click tag allows ligation with a cell penetrating peptide (CPP) using bioorthogonal chemistry, thus triggering translocation. The synthesis of relevant building blocks (bioorthogonal functional groups, linkers, chelators), conjugation reactions to the TTA and CPP, as well as a preliminary in vitro evaluation are described.