Preclinical studies on nanocarrier-mediated delivery of radiosensitizing agents to brain and pancreatic cancer with a future projection to liver cancer

Radiotherapy is one of the main treatment modalities in oncology. The therapeutic effectiveness of irradiation is dependent on the balance between the tumour control probability (TCP) and the normal tissue complication probability (NTCP), i.e. the induction of side effects. Combination treatment of irradiation with chemotherapy, targeted or immune-modulating agents could significantly benefit from nanotechnology strategies, allowing localized delivery of therapeutic compounds to the irradiated tumour volume. When used in combination with irradiation, drugs should be selected on their interaction with the 6 R’s, the six Hallmarks of Radiobiology, to sensitize for the radiation effect on the molecular, cellular and tissue level, and therewith positively impact the TCP/NTCP balance. In this chapter, preclinical data on the combination of irradiation and nanocarrier delivered drugs in brain, pancreatic, and liver cancer are presented and discussed. Before implementation into the clinical practice, nanotechnology demands for further technical and biological studies on topics such as drug loading efficacy, drug release, cellular and tissue uptake, biodistribution, tumour targeting methods and administration routes to the patient. Notwithstanding those challenges, the combination of local radiotherapy with tumour targeted nanocarrier delivered radiosensitizers as well as the use of radiosensitizing nanoparticles are exciting developments with great clinical prospect.