# Doped Zinc Oxide Nanoparticles: Synthesis, Characterization and Potential Use in Nanomedicine
## 1 Introduction
In the specific case of ceramic materials and metal oxides, some examples include: mesoporous silica nanoparticles as nanocarriers in drug delivery systems [46; 47] and as bioactive agents for bone tissue engineering [48]; cerium oxide nanoparticles featuring antibacterial and antioxidant therapeutic properties [49; 50; 51]; magnetic iron oxide nanoparticles, which were successfully proposed as theranostic nanvectors coupling therapeutic effects against cancer cells through hyperthermia with MRI contrast agent properties [52; 53; 54]. More recently, the use of zinc oxide (ZnO) in nanomedicine captured considerable attention [55]. ZnO is a low-cost, abundant material, classified as a generally recognized as safe (GRAS) material from the Food and Drug Administration [56], which makes it suitable for a plethora of biomedical applications. Moreover, ZnO is a wide band-gap semiconductor (3.37 eV) featuring peculiar physical and chemical properties, such as photo- and sono-catalytic activities [57; 58; 59], piezoelectricity [60; 61] and pyroelectric [62] behaviors. The abovementioned properties can be combined together and even strengthened by selecting, among the numerous ZnO morphologies, the most appropriate one: thin films [63; 64], nanowires (NWs) [65], nanorods (NRs) [66], nanobelts [67], nanoparticles (NPs) [68] and flower-like structures [69] can be easily synthesized by wet and dry preparation approaches such as sol-gel and hydrothermal routes, and vapor-phase deposition techniques. Various ZnO nanomaterials have been successfully applied in TE [70]. ZnO NWs [71], NRs [72] and nanoflowers [73] have been found to promote the adhesion, growth, and differentiation of several cell lines. ZnO NPs can be easily addressed in the human body due to their reduced size, which also facilitates cellular uptake [74]. Therefore, the promising osteogenic and angiogenic properties of ZnO NPs have been demonstrated, along with their use as nanotherapeutic agents to fight bacterial infections [75; 76]. In this sense, ZnO NPs are defined as nanoantibiotics due to their promising antimicrobial properties against both Gram-positive and Gram-negative bacteria. ZnO nanomaterials as targeted drug delivery systems have been reported as well [77; 78; 79]. ZnO QDs (2-10 nm) were combined with doxorubicin-loaded Mesoporous Silica Nanoparticles (MSNs) and used as nanolids to cover silica nanopores and achieve a sustained and pH-triggered delivery of the anticancer drug [80]. Other works include the use of mesoporous ZnO nanospheres [81], dandelion-like mesoporous ZnO capsules [82] and porous hexagonal ZnO nanodisc structures [83]. In the latter cases, the targeted and pH-triggered delivery of chemotherapeutic agents against cancer cells was effectively demonstrated. ZnO nanoparticles have been also used as imaging agents [79] for cell labeling [84], tumor targeting [85] and diagnostics [86]. ZnO NPs can also serve as a nanodrug to treat cancer cells [87; 68; 88]. The therapeutic effect is accomplished by the release of harmful species (Zn\({}^{2+}\) cations and reactive oxygen species, ROS) upon interaction of ZnO with aqueous media [89; 90; 91]. The therapeutic efficacy of ZnO NPs against different cancer cell lines was confirmed in vitro. In some cases, the remote activation of ZnO NPs cytotoxicity has also been obtained. It is the case of photodynamic [92] and sonodynamic [89; 93] therapeutic approaches, an external stimulus (a light or mechanical one) was able to activate the cytotoxic effect of the nanotherapeutic drug, i.e., the ZnO NPs themselves, which could generate a harmful ROS or mechanical damage to cancer cells. Despite the promising results, the use of ZnO nanomaterials in nanomedicine is still limited because of some intrinsic limitations such as a low stability of the ZnO particles in biological fluids and the non-controllable release of Zn\({}^{2+}\) cytotoxic species [94; 95]. Hence, additional efforts are required to make ZnO more attractive.