# Doped Zinc Oxide Nanoparticles: Synthesis, Characterization and Potential Use in Nanomedicine
## 3 Synthesis Methods and Characterization
### Wet Chemical Methods
Briefly, zinc acetate and copper (II) acetate monohydrate were dissolved in water, and NaOH aqueous solution was then added to the solution until a gel formed. Differently from the co-precipitation and sol-gel techniques previously discussed, in this case the gelled solution was placed in an autoclave at 160 \({}^{\circ}\)C for 5 h to get the formation of the ZnO:Cu powders. The as-prepared Cu-doped nanoplates exhibited variable dimensions of few hundreds of nm, as shown in Figure 5. Additionally, in this case, the dopant agent slightly increased the unit cell volume of the ZnO crystal. Cu-doped nanoplates were tested in terms of their antimicrobial properties against _E. coli_ and _S. aureus_, showing a decrease in the minimum inhibitory concentration (MIC) with respect to pure ZnO (Figure 5). Figure 5: SEM images and antimicrobial performances of Cu- and Ag-doped nanoplates. Adapted from ref. [152]. Silver is a noble metal widely explored for antimicrobial applications due to the action of Ag\({}^{+}\) on bacterial membranes [186]. Therefore, it was considered as a TM element to prepare antimicrobial Ag-doped ZnO nanoparticles. A study going in this direction is reported by [PERSON] et al., in which zinc acetate and silver nitrate were chosen as precursors, while ammonia was used as agent for inducing particle precipitation [165]. In addition, in this case, Ag doping induced a shift in the diffraction pattern toward higher angles with the increase of the doping amount. Other metals such as magnesium, lithium and aluminium were used for doping ZnO nanoparticles by wet chemical synthesis. For magnesium, the enhanced photocatalytic activity of Mg-doped ZnO nanoparticles with respect to their pure counterparts was reported [138]. The doped nanoparticles were prepared by a co-precipitation method and the effective insertion of an Mg dopant in the host ZnO crystal lattice was confirmed by XRD which highlighted an increase of the volume of the unit cell. With regard to lithium doping, a work reported its use in enhancing the photoactivated ROS generation of ZnO when using this system for anticancer therapy [144]. In this work, zinc acetate dihydrate and lithium acetate dihydrate were used as precursors in a polyol synthesis performed in triethyleneglycol (TREG) as the solvent. Finally, Al-doped ZnO (AZO) nanoparticles were synthesized by a wet chemical method and their antibacterial performances were studied. Zinc nitrate hexahydrate was mixed with the aluminium precursor (aluminium nitrate nonahydrate) for the oxide synthesis [187]. Among wet chemical syntheses, the reverse-micelles microemulsion method was also explored for the preparation of doped ZnO nanoparticles [188]. The presence of specific surfactants by this approach can lead to peculiar ZnO morphologies, such as hollow structures [189], and can also limit the dimensions of the particles during nucleation. For example, the reverse-micelles method has been successfully exploited to develop Eu-doped [190, 191] and Mn-doped [192] ZnO nanorods and nanoparticles with a controlled size. In particular, in the case of europium-doped nanoparticles, it is possible to obtain either very small nanospheres with an average diameter of about 5 nm, or nanorods with lengths of some hundreds of nanometers and a diameter of some tens of nanometers, by changing precursors (Zn(CH\({}_{3}\)COO)\({}_{2}\cdot\)2H\({}_{2}\)O and Eu(CH\({}_{3}\)COO)\({}_{3}\cdot\)4H\({}_{2}\)O for nanospheres and ZnCl\({}_{2}\) and EuCl\({}_{2}\) for nanorods), oils and surfactants (sodium bis(2-ethylhexyl) sulfosuccinate and heptane for nanospheres and octane, CTAB (cetyltrimethyl ammonium bromide) and butanol for nanorods). As a summary, it may be stated that wet chemical methods are the mostly exploited ones for the development of doped ZnO nanoparticles. The main advantages of these techniques are the simplicity of the process and the wide variety of morphologies obtainable. Table 2 summarizes the main aspects of some of the techniques used to synthesize doped ZnO nanoparticles.