## 3 Biomedical Applications of Yttrium Oxides Nanoparticles
### Anticancer Activity  
In addition, antimicrobial, antibacterial, and antioxidant Y\({}_{2}\)O\({}_{3}\) NPs exhibited a predominant anticancer ability. The preparation of NPs using natural products has attracted remarkable and increased interest, due to its unmatched resources, inexpensive nature, and as an alternative to chemicals with non-toxicity and offering no biological risk [95] or side effects. Recently, [PERSON] et al. [83] have demonstrated the synthesis of NPs using _Liriope platphylla_ rhizome extract with a size of 17 nm that reportedly exhibited anticancer activity. Similarly, [PERSON] et al. [39] have reported Y\({}_{2}\)O\({}_{3}\) synthesis involving _Forsythiae fructus_ aqueous fruit extract and validated its anticancer ability against kidney cancer cell lines, such as Madin-Darby Canine Kidney (MDCK) and Caki-2. The results showed a flake-like flower appearance of NPs with a size of 11 nm. The toxicity effect reveals that NPs exhibited no toxic effect on the normal MDCK cells, while more toxicity to renal cancer cells in high concentration was reported in Figure 5.  
[PERSON] et al. [96] have suggested the combined effects of Y\({}_{2}\)O\({}_{3}\) and cerium oxide protected beta-cell apoptosis by accelerating the oxidative stress-dependent apoptotic pathway. In tissue engineering, Y\({}_{2}\)O\({}_{3}\) finds other applications in which metal oxide (Y\({}_{2}\)O\({}_{3}\)) NPs are embedded in polyacrylamide (PCL) scaffolds to enhance the proliferation of endogenous cells, and exhibited angiogenic properties. The findings of the experiment reported that the presence of Y\({}_{2}\)O\({}_{3}\) in the scaffolds upregulates the cell expression of proliferation-associated molecules, like vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). The study concluded that Y\({}_{2}\)O\({}_{3}\) NPs play a crucial part in tissue engineering scaffolds to induce proliferation and angiogenesis. NPs offer cytoprotection to healthy cells from ROS impacts. However, they attract and kill cancer cells using enhanced ROS generation. Cancer cells possess an acidic microenvironment, due to its series of biochemical reactions, such as glycolysis, and produced lactic acid accumulation [97] prevailed. Polyethylene glycol methacrylate phosphate (Poly-EGMP) yttrium NPs proved to be safe up to 0.1 mg/g body weight in 1-month-old Sprague-Dawley rats, showing also the ability to cross the blood-brain barrier a short time after tail injection.  
Figure 5: **(a)** Microscopic images of Madin-Darby Canine Kidney (MDCK) and Caki-2 cells. **(b)** Cytotoxic effect of Y\({}_{2}\)O\({}_{3}\) NPs on MDCK and Caki-2 cells by SRB assay at 24 h. Values were expressed as means \(\pm\) mean standard error (MSE). **(c)** Effect of Y\({}_{2}\)O\({}_{3}\) NPs on the Caki-2 cells discriminated by Fluorescein diacetate (FDA) and propidium iodide (PI). Area R3 is FDA positive, R5 is PI-positive, R4 is both FDA and PI-positive, and R2 is both FDA and PI negative. Effect of Y\({}_{2}\)O\({}_{3}\) NPs on Caki-2 cell viability was examined at 24 h (Reprinted with permission from [39]).  
The surface modification of yttrium NPs here described allows these NPs to be potentially used in theranostics to reduce neurodegenerative damage due to heat stress [98]. Non-cationic nanomaterials that adsorb DNA but cannot quench fluorescence are less known. These materials are attractive for studying the mechanism of DNA-based surface reactions. Y\({}_{2}\)O\({}_{3}\) was found to have this property and it has been used for fluorescently labeled oligonucleotides as probes to study the mechanism of DNA adsorption [99]. Therefore, Y\({}_{2}\)O\({}_{3}\) is a potential option for inhibiting the growth of cancer cells.