## 3 Surface Functionalization  
Promising biomedical applications can be achieved through surface functionalization of the magnetic core. As has already been discussed, the surface features of nanoparticles are important aspects that must be considered in functionalization. Based on these assumptions, significant progress has been made in the preparation of magnetic nanoparticles with specific properties for certain biomedical applications. Such examples include stabilization agents such as chelating organic anions (citric acid, palmitic acid, gluconic acid, oleic acid, amino acid [123; 124]), inorganic shells--metal or metal oxides (copper, silica)--or polymeric agents such as dextran, alginate, chitosan, etc. [125], as presented in Figure 2.  
Figure 2 is a representation of surface functionalization in developing both dense and porous core@shell structures. Under certain conditions, a combined approach can be used, such as the core@shell@shell structures, such as even Fe\({}_{3}\)O\({}_{4}\)@SiO\({}_{2}\)@mSiO\({}_{2}\) core@shell@shell developed by [PERSON] et al. [75] from Fe\({}_{3}\)O\({}_{4}\) and two layers of silica, the internal one being dense, while the exterior is mesoporous. Many biomedical applications are reported for mesoporous silica, as well as for the diagnosis and treatment of cancer and diabetes [126],  
Figure 2: Surface stabilization protocols in developing porous versus non-porous core@shell magnetic nanostructures. thus offering the premises that, for these Fe\({}_{3}\)O\({}_{4}\)@SiO\({}_{2}\)@mSiO\({}_{2}\) core@shell@shell structures to be used in such applications, the core must be additionally protected. The Fe\({}_{3}\)O\({}_{4}\)/SiO\({}_{2}\) core-shell nanocubes have good biomedical applications and their loading with streptavidin, the most common globular protein used in imaging, detection, drug delivery, and surface modification, has confirmed the ability of these nanocubes to bind to biomolecules. Furthermore, the stability of core-shell nanostructures is critical in practical applications, the core-shell Fe\({}_{3}\)O\({}_{4}\)/SiO\({}_{2}\) nanocubes preparations have been examined and the tests confirmed the stability of core/shell nanocubes against severe conditions by reconstructing the samples coated in the presence of gaseous hydrogen [45,114]. Another important aspect that needs to be taken into consideration, especially from the bio-applications point of view is biocompatibility, and studies in HeLa cells have shown good biocompatibility. In conclusion, the Fe\({}_{3}\)O\({}_{4}\)/SiO\({}_{2}\) core/shell nanocubes, where magnetite nanocubes have been coated with uniform silica shells, make them suitable nanostructures for biosensing applications [12]. In the work conducted by [PERSON] et al. [57], stable magnetic nanoparticles of controllable particle size were successfully synthesized with high efficiency in hyperthermia applications. These results concluded that good heating rate and surface functionalization are a perfect synergy that helped to develop a nanomaterial with magnetic properties for biomedical applications, which are influenced by their surface characteristics [4,53]. To use magnetic nanoparticles in biomedical applications, it is necessary to be able to present tuneable surface characteristics. The literature provides many magnetic nanoparticles with great applications; however, the surface coating is highly studied to improve their required properties [41]. As is well known, the functionalization of silica-based materials can occur easily and lead to significant improvements from both loading and release capacity. In this attempt, Fe\({}_{3}\)O\({}_{4}\)@SiO\({}_{2}\) was functionalized by linking amino moieties, and these nanostructures can be further used for the immobilization of \(5^{\prime}\)-nucleotidase enzyme to detect cancer biomarkers. Therefore, [PERSON] et al. [127] developed magnetite nanoparticles to separate the \(5^{\prime}\)-nucleotidase enzymes (SeNT).