Cancer Imaging And Treatment

About

What is the problem? Radiotherapy and chemotherapy agents act by introducing high levels of DNA damage within the DNA of tumour cells. However, DNA repair machinery, which is present in all cells, repairs this damage, increasing the probability of tumour cells to survive the treatment and proliferate. Any treatment that additionally reduces and prevents the cellular DNA repair capacity is a valuable complementary cancer therapy. Introducing inhibitors of DNA repair to increase the efficacy of DNA-damaging anticancer drugs is considered a promising strategy for novel cancer treatments. Nonetheless, the outstanding progress in the understanding of fundamental cancer biology and DNA damage responses of the past decades was not accompanied by comparable advances in the clinic. For example radiation therapy in humans benefited much more from technical progress and computerization rather than from knowledge-based manipulation of the biological responses of cancer cells to therapeutic radiation. Our new Solution? Novel nanoparticles which introduce chemo-sensitising or radio-sensitising compounds into the nucleus of the cancer cell acting as DNA repair inhibitor and nuclear localisation signal element. Benefits of the new technology Chemotherapeutic agents, DNA repair inhibitors and radio therapy can be more accurately targeted to cancer cells, can be used in combination with a wide range of existing radiotherapy and chemotherapy treatments to increase their effectiveness, improved efficancy w.r.t. radiation therapy alone: up to an order of magnitude higher, elemental images of whole cells with an unprecedented definition and elemental sensitivity down to attogram of metal in cells, potential reduction of drug resistance, non-toxicity. Background DNA repair inhibitors in cancer cells have the potential to significantly increase the effectiveness of existing radiotherapy and chemotherapy treatments at killing tumours. With the aim of being able to manipulate DNA damage responses in cells following the therapeutic intervention, the most desirable target is the nucleus. This is because the dose-enhancement of ionizing radiation by high-atomic number materials such as gold and platinum is dependent on the close proximity to the DNA due to short predicted distances travelled by the secondary electrons responsible for the effects. The local inhibition of DNA repair mechanisms close to the site of DNA damage is also likely to have a much more pronounced effect on the cell survival. Targeted nuclear delivery is a challenging problem but we have developed functionalized non-toxic nanovectors which are able to: Translocate to the cell nucleus and inhibit the DNA damage/repair responses in the targeted cells, increase the sensitivity of targeted cells to therapeutical radiation by inhibiting DNA double strand break repair, decrease the clonogenic survival by up to an order of magnitude, assist in localisation of the nanoparticles close to the DNA.