# Quantum Leap from Gold and Silver to Aluminum Nanoplasmonics for Enhanced Biomedical Applications
## 2 Aluminum Plasmonics
### Treatment Mechanisms
#### 2.2.4 Toxicity  
Toxicity of metallic NPs has been widely studied and was shown to be inversely dependent on the NP size [77; 78]. The effects of Au, Ag, and Al NPs on human cells and tissues have been investigated [79]. Even though the bulk Au and Ag are generally considered to have minimal effects on health, the long-term effects of bulk Ag exposure can cause argyrosis [80]. However, several adverse effects may be caused by Au and Ag NPs, which need to be taken into consideration when applying the treatment on the human body. For example, Ag has been widely used for antibacterial treatment and disinfection [81] and Ag NPs play a crucial role in healing and treatment within the biomedical field [82]. However, with the diversity in applications such as wound and burn treatment, surgical equipment disinfection and drug-delivery, Ag NPs can enter the human body through various ways. The translocation of Ag NPs into various organs in rats was shown [61]. The toxicity of Ag NPs was shown via measurements of cell viability, reactive oxygen species (ROS), or lactate dehydrogenase (LDH) leakage [83]. The viability of mesenchymal stem cells (MSCs) was decreased [84] and lung tissue damage on animal studies was revealed due to the oxidative stress [85] after exposure to Ag NPs, supporting the high toxicity of Ag NPs and presenting a potential risk to human health.  
On the other hand, several studies also indicated the absence of toxicity of Ag NPs to certain types of cells. It was shown that 20 and 80 nm diameter Au and Ag NPs had lower toxicity to human embryonic neural precursor (HNPC) cells compared to AgNO\({}_{3}\), but still affected the growth of HNPCs [79]. Au NPs have lower toxicity compared to Ag NPs. Surface functionalization may affect the toxicity of NPs. For example, Au NPs with cationic trimethylammonium ligands showed cytotoxicity even at a low concentration of Au NPs [86]. On the other hand, many examples of noncationic Au NPs at high concentrations showed the absence of cytotoxicity [87; 88]. The toxicity of metallic NPs depends on many factors such as NP size, shape, and surface functionalization, which may be optimized to improve the performance of NPs. Size of Au NPs determines the translocation and NP localization within the body [89].  
Even though the toxicity of the alumina (Al\({}_{2}\)O\({}_{3}\))-based NPs has been studied [90], there has been limited research on the toxicity of Al NPs. Compared with Ag and Au NPs, the Al NPs are expected to have lower cytotoxicity. However, in several cases of high doses, Al NPs have shown some adverse effects. Al NPs reduced the viability of rat alveolar macrophages and limited phagocytic function [91]. It was shown that Al NPs may have a higher level of cytotoxicity compared to that of Al\({}_{2}\)O\({}_{3}\) NPs [91].  
In summary, the estimation of the effectiveness of the NP treatment considers toxicity, which, depending on the application, may be optimized by the choice of the chemical composition and morphological parameters. Al NPs, in general, have low toxicity, which could be minimized by increasing the treatment efficiency using the thermal, UV, and hot electron mechanisms described above, reducing the concentration of NPs required to achieve effective treatment.