The capacity of pharmaceutical agents to selectively find their biological targets is an important determinant of their usefulness in clinical medicine. Many pharmaceutics are directed against intracellular targets that reside in organelles. Carriers that selectively target these subcellular structures have been investigated, and include nanoparticulate drug carriers, chemically modified proteins and deoxyribonucleotide-based agents. As well as the nucleus, the mitochondria, endoplasmic reticulum, Golgi-complex, the lysosomal system have all been investigated as intracellular targets of irradiation. There is increasing evidence that the nucleolus, the site of ribosomal assembly, plays an important role in sensing and orchestrating the response to cellular stresses including that which occurs in response to radiation. Therapeutic strategies that specifically hamper nucleolar function are being investigated in cancer and may be particularly effective in combination with radiotherapy. The initial central aim of this project will be to develop nucleolar-targeting oligonucleotide-based agents aimed at causing nucleolar functional disruption and radiosensitisation. Direct delivery of radiation to nucleolar sites using oligonucleotide-based radionuclide-labelled compounds will also be tested.