# Co-Adjuvant Nanoparticles for Radiotherapy Treatments of Oncological Diseases
## 3 Nanoparticles in Radiotherapy
### Active Nanoparticles and Catalysts Inducing ROS Generation  
As extensively explained above, the augmented photoelectric effect cross section in presence of NPs with heavy Z enables the creations of secondary charges, mostly Auger electrons, and the productions of direct and indirect DNA cancer cells damages. However, as reviewed by [PERSON] et al. in Ref. [104], there are many evidences that also metal oxide NPs with lower atomic number (made up by Si, Al, Ti, Zn, Fe, Ce and Mn for instance) are responsible of radiosensitization phenomena within tumor cells. This output is imputed to the chemical and catalytic activities of the NPs surfaces contributing to the overall generation of radiation-induced radicals. From a general point of view, nanocatalysts are materials able to produce ROS under high energy light (photocatalysts) and ionizing radiation (radiocatalysts) to decompose unwanted chemical and biological agents. Despite the attempt to treat the radiocatalysis as similar to the well-known photocatalysis [65], it is worth to notice that the use of ionizing radiation guarantees diverse advantages, such as the increased rate of a catalytic reaction, the acceleration of degradation of pollutants, the overcoming of limited penetration of UV/Visible (Vis) light in solutions and biological tissue, as well as the possibility to use a wider range of catalyst also with wider band gap (E\({}_{\text{g}}\)) and greater redox capabilities [105; 106; 107]. If we consider the case of (nano) titanium oxide, TiO\({}_{2}\), as representative of photo-/radiocatalysis in semiconductors, catalysis phenomenon can be summarized in the following steps: (1) excitation by high energy ionizing radiation or light source with energy larger than the E\({}_{\text{g}}\) of the material; (2) promotion of an electron (e\({}^{-}\)) from the valence band to the conduction band, and the concomitant generation of a hole (h\({}^{+}\)) in the valence band; in an efficient nanocatalyst, where recombination of the generated e\({}^{-}\)/h\({}^{+}\) is restrained, the last step (3) is the diffusion of e\({}^{-}\)/h\({}^{+}\) charges towards the materials surface to rapidly (in sub-nanoseconds time range) initiate redox reactions among reactants adsorbed at the nanocatalyst surface, and to start the formation of ROS. In presence of aqueous environment, electrons reduce molecular oxygen forming superoxide radical anion; hydroxyl radicals and hydrogen peroxide molecules are induced by the holes oxidizing water molecules and hydroxide ions. In TiO\({}_{2}\), it has been also proven the occurrence of singlet oxygen creation (\({}^{1}\)O\({}_{2}\)) after oxidation of superoxide radical ion [108, 109, 110]. The reactive species, especially hydroxyl radicals, can be used to decompose a variety of pollutants in environmental applications [111]. More important for the goal of this review is the effective damage that the generated ROS can produce on DNA of cancer cells and biomolecules, thus contributing to the biological damage induced during radiotherapy, as well as to the lethal prolonged metabolic oxidative stress after irradiation [112]. Due to the large active surface area, it has been established the importance of morphological features (e.g., size, composition, specific surface ligands, surface charges) on the amount of ROS generated by NPs [113]. Numerous examples in the literature report chemistry strategies to fix up the NP surface properties also through functionalization/coating procedures [114, 115]. In this review, we aim at providing straightforward examples illustrating the importance to conduct further research on lower Z radiocatalysts, whose effect in reducing cancer growth in RT is as effective as the one of high Z and dense NPs, thanks to the boosted ROS productions. We consider two well-known radio-photocatalyst NPs, specifically titanium and zinc oxide (TiO\({}_{2}\) and ZnO, respectively), which have been approved by Food and Drug Administration (FDA) [116].