# Doped Zinc Oxide Nanoparticles: Synthesis, Characterization and Potential Use in Nanomedicine
## 4 Use of Doped ZnO NPs in the Biomedical Field
### Antimicrobial Agents
coli_), and Gram-negative ones such as _Staphylococcus aureus_ (_S. aureus_) [234; 235]. Figure 9: Schematic reporting the main ZnO toxicity mechanisms that make this material an effective antimicrobial agent. Adapted from ref. [232]. Doping has been demonstrated as a useful tool to tailor the antimicrobial properties of ZnO nanoparticles. Indeed, the generation of antibacterial reactive oxygen species from the customization of the optical properties due to ZnO doping can be an advantage. Some improvements in the photocatalytic properties and photoexcitation efficiency, which are the main mechanism through which antimicrobial ROS are generated in ZnO-based systems, were found in several works by using different doping agents [138; 143; 185; 209]. For example, silver is a possible choice in terms of dopants which are useful for increasing the antibacterial activity of ZnO. The reason lays in the intrinsic bactericidal activity of silver ions against a wide spectrum of bacteria typologies [186]. As shown in the work of [PERSON] et al., ZnO structures with large surface area morphologies and doped with different Ag amounts were tested against different microorganisms (bacteria, yeasts and fungi) [233]. Disk diffusion tests highlighted that hexagonal ZnO particles were effective in contrasting microorganism growth when pure ZnO was used. However, Ag doping was found to be efficient in boosting the antibacterial properties (with an optimal doping value of 0.05 mol.%) against most of the tested biological species, resulting in a broad spectra antimicrobial device. Another work reported the comparison between pure, gold- and silver-doped ZnO nanoparticles synthesized by a combustion method [134]. The photocatalytic efficiency resulting from the degradation of methylene blue under UV exposure was proven to be higher for the doped particles. In particular, Ag-doped ZnO NPs reached a 45% methylene blue degradation efficiency after 160 min against a 25% efficiency for Au-doped ZnO and 8% for undoped ZnO. This result was attributed to the noble metal clusters formed on the surface of ZnO nanoparticles during synthesis, which inhibited the recombination of the photogenerated electron/hole pairs. However, the antibacterial activity against _E. coli_ and _S. aureus_ was lower for doped ZnO with respect to the pure counterpart. On the contrary, Ag doping was effective against _E. ashbyii_, even if a direct comparison with other doped ZnO systems was difficult because of the presence of dopant clusters rather than a correct inclusion of dopant atoms in the ZnO crystal lattice. In the work by [PERSON] et al. [165], ZnO particles were successfully doped, including Ag ions into the crystal lattice and a reduction of the minimum inhibitory concentration (MIC) was found for _S. aureus_ with respect to pure ZnO, in contrast to what was found in the previous work. Silver doping was also compared to copper doping in terms of antimicrobial activity. Hydrothermally synthesized undoped, Cu- and Ag-doped ZnO nanoplates were tested against _E. coli_, _S. aureus_ and _Salmonella typhi_ by a well diffusion method in order to determine the MIC [152]. The results reported an increased bactericidal activity of both doped ZnOs, the result of a decreased MIC. Moreover, Ag-doped nanoplates were more efficient than Cu-doped ones. In this work, the authors also highlighted the role of light. The antimicrobial properties of the doped ZnO nanostructures were limited when the bacterial seeding and treatment processes were performed in dark conditions, suggesting that the photoexcitation of the semiconductor plays an important role in determining the antimicrobial activity of ZnO. Cu-doped ZnO nanoparticles were analyzed in terms of antibacterial activity in another study. A green combustion method was followed to synthesize the nanoparticles, which were tested against _E. coli_, _S. aureus_, _Bacillus subtilis_ and _Klebsiella_ through the agar diffusion method [236].