# Co-Adjuvant Nanoparticles for Radiotherapy Treatments of Oncological Diseases
## 3 Nanoparticles in Radiotherapy
### Active Nanoparticles and Catalysts Inducing ROS Generation
In nanomedicine, the ability of ZnO and TiO\({}_{2}\) in producing ROS by themselves under UV/Vis excitation has been exploited for the photodynamic therapy [117]. Indeed, PDT is considered as a clinically deployed efficient and non-invasive alternative to the surgery and to the current oncological therapies. PDT is based on the cytotoxic effects originating when biocompatible photosensitizers (PSs) are photoexcited, producing ROS and singlet oxygen moieties that induce the cell death through oxidative damage of cellular membranes [118]. PSs can include organic dyes and aromatic hydrocarbons, porphyrins and related photosensitizers, transition metal complexes, and semiconductors [119]. Unfortunately, the PSs approved for routine PDT treatment require UV/Vis light to be activated. In this spectral region, the human tissue transparency is low, thus making PDT ineffective for tumors seated at depths larger than 1 cm [120]. Interestingly, TiO\({}_{2}\) and ZnO have been proved to create ROS also under ionizing radiation and to be suitable for X-ray based oncological treatments. For instance, a work of [PERSON], [PERSON], et al. reports the radiosensitization phenomenon in presence of anatase TiO\({}_{2}\) NPs under X-ray beam with energy set from keV to MeV [121]. Tests on cell viability assays have been performed on phantoms and in vitro to determine cells survival curves and the dose enhancement percentage. The obtained results evidence the occurrence of sensitization driven by two different mechanisms: in the keV range, the photoelectric effect coupled to the difference in the atomic numbers of the biological tissue and the TiO\({}_{2}\) NPs are responsible of the dose enhancement; when MeV energy is used, the cross section of the photoelectric effect decreases while the active catalytic surfaces of the NPs start to play the major role in the generation of cell killing ROS, leading to the final therapeutic sensitization of RT. The possibility to take advantage of the two mechanisms, i.e., photoelectric and Z-dependent radiosensitization, together with the generation of ROS capable of destroying tumor cells by nanocatalysts, is at the base of the development of novel composite materials, like Au nanoparticles supported on TiO\({}_{2}\) (Au@TiO\({}_{2}\)), enabling the simultaneous and synergetic establishment of the two processes, which lead to superior performances over the single elements [122]. Nanoparticles of ZnO are attractive materials for biomedical applications due to noticeably low toxicity. ZnO NPs have been widely explored for anticancer, antidiabetic, antibacterial, antifungal, and anti-inflammatory activities, as well as for drug delivery applications. Especially, ZnO NPs anticancer action relies on their ability to trigger ROSgeneration and apoptosis mechanisms under external excitations. Recently, the X-ray radiation-induced therapeutic behavior of ZnO NPs coated by a silica layer (ZnO/SiO\({}_{2}\)) has been studied on prostate adenocarcinoma cell lines. The potentiality of ZnO/SiO\({}_{2}\) nanoparticles to increase radiation-induced killing of the cells has been validated by comparing cells survival after RT with and without NPs. Results display a 2-fold augmented killing rate in presence of ZnO based NPs; the findings show the active response to ionizing radiation of ZnO/SiO\({}_{2}\) by means of the radiocatalytic mechanisms occurring at its surface. The proven catalytic reactions induced by high energy radiation make ZnO/SiO\({}_{2}\) nanoparticles suitable for biomedical applications [123]. The combined use of ZnO with chemotherapeutics represents a step forward in the use of ZnO as anticancer. The loading of the anticancer drug, like doxorubicin as in ref [124], into the ZnO nanoparticles, results in an augmented cytotoxicity effects of the cancer therapy, due to the simultaneous combination of the anticancer action of the drug with the lethal ROS production by ZnO.