Preclinical Studies on Nanocarrier-Mediated Delivery of Radiosensitizing Agents to Brain and Pancreatic Cancer with a Future Projection to Liver Cancer

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Radiotherapy is one of the primary treatment modalities in oncology. Thetherapeutic effectiveness of irradiation is dependent on the balance between the tumorcontrol probability (TCP) and the normal tissue complication probability (NTCP), i.e.,the induction of side effects. Combination treatment of irradiation with chemotherapytargeted to a tumor or using immune-modulating agents could significantly benefitfrom nanotechnology strategies, allowing localized delivery of therapeutic compoundsto the irradiated tumor volume. When used in combination with irradiation, drugsshould be selected on their interaction with the 6 R's, the six Hallmarks ofRadiobiology, to sensitize the radiation effect on the molecular, cellular, and tissuelevel, and in addition to that, positively impact the TCP/NTCP balance. This chapterpresents and discusses preclinical data on the combination of irradiation andnanocarrier-mediated delivery of drugs in the brain, pancreatic, and liver cancer. Beforeimplementation into the clinical practice, nanotechnology demands further technicaland biological studies on drug loading efficacy, drug release, cellular and tissue uptake,biodistribution, tumor-targeting methods, and administration routes to the patient.Notwithstanding those challenges, the combination of local radiotherapy with tumortargetednanocarrier-delivered radiosensitizers, as well as the use of radiosensitizingnanoparticles, are exciting developments with a great clinical prospect.