# Doped Zinc Oxide Nanoparticles: Synthesis, Characterization and Potential Use in Nanomedicine
## 4 Use of Doped ZnO NPs in the Biomedical Field
### Doped ZnO as Therapeutics against Cancer
Then, the cells viability was evaluated by an MTT assay, giving the results reported in Figure 12. In dark conditions, the NPs only slightly decreased the cells' viability with the increase of the concentration, demonstrating that Gd- and Eu-doped ZnO nanoparticles did not induce considerable cell death. However, when UV exposure was considered, the cells viabilities heavily reduced for all the doped and undoped-treated cell cultures, suggesting the importance of the photoexcitation of the ROS production. Another important aspect was a remarkable selectivity in killing only cancerous cells if intermediate concentrations of doped ZnO particles (10 \(\upmu\)g/mL) were used. Cell lines incubated with ZnO NPs were also exposed to X-rays and \(\gamma\)-rays. While \(\gamma\)-rays did not give important changes in the viability of cells with respect to dark conditions, X-rays at 2 Gy were extremely effective at killing cells, with doped ZnO NPs in particular, perhaps because of a higher ROS generation. Figure 11: Photodynamic therapy mechanism. The photosensitizer (PS) is excited by external radiation, the excited electron may decay through different phenomena which may end in the generation of cytotoxic species, like ROS. Adapted from ref. [284]. Gadolinium doping coupled with X-ray radiation was tested also in another study, where Gd-doped ZnO nanoparticles were administered to lung carcinoma cells (SKLC-6) and irradiated with megavoltage X-rays [286]. Nanoparticles with a dimension of 9 nm were successfully internalized in the cell bodies as shown in Figure 13. A dose-dependent effect under X-rays irradiation was observed also in this case; the cells viability decreased when the NPs concentration was increased, reaching \(\sim\)20% of cell viability with respect to the control at 100 \(\upmu\)g/mL of the NPs concentration, as well as a reduction in the DNA repair efficiency. Additionally, Mg-doped ZnO nanoparticles were proven to induce cell death in human breast cancer cells (MCF-7), and AO & EB staining coupled with fluorescence microscopy showed that the main way through which cell died was apoptosis [166]. Cu-doped ZnO nanoparticles synthesized by a green method demonstrated similar anticancer properties [236]. The comparison on the cell viability between pure ZnO NPs, Cu-doped ZnO NPs and doxorubicin showed superior cytotoxic effects of the doped NPs against breast cancer cells. The proposed mechanism for cell death was the penetration of the small particles through the cell barrier. Figure 12: Cell viability of different cell lines exposed to different illumination sources and different concentrations, incubated with pure, Gd-doped and Eu-doped ZnO nanoparticles. Adapted from ref. [164]. Figure 13: TEM images showing the internalization of pure (**a**) and Gd-doped (**b**) ZnO nanoparticles in lung carcinoma (SKLC-6) cells. Adapted from ref. [286]. Despite ZnO being already proposed as a therapeutic agent against cancer, doped ZnO nanoparticles still do not have a large literature pool through which the mechanism of toxicity can be stated univocally. Many studies have reported an increased cytotoxicity in concomitance with increased photocatalytic and antibacterial activities. Other works focused on the stability of the ZnO particle to tune specifically the antitumoral effect. Even if further studies are required, the results herein described clearly show that doped ZnO can be a powerful weapon to fight cancer.