## 2 Synthesis of Magnetic-Silica Core/Shell Structures  
The most stated synthesis method for magnetite-silica core/shell nanostructures is the Stober sol-gel method, which is a chemical synthesis route used to prepare silica shells of controllable and uniform size over the magnetite nanoparticle acting as a core [71]. The introduction describes the SPIONs as superparamagnetic iron oxide nanoparticles for biomedical applications. Besides the synthesis methods of the magnetite-silica core/shell structures, the process synthesis for SPIONs was also introduced. The literature [33; 72] illustrates the synthesis methods for SPIONs such as gas deposition, thermal decomposition, hydrothermal, and other methods which have distinct procedures and different conditions for each type of nanoparticles. For SPION synthesis, the most used methods are co-precipitation and thermal decomposition [33]. It is important to mention that core/shell magnetic structures are developed to combine the advantages of the two layers; the magnetic one is responsible for the magnetic properties, while the shell ensures greater stability and can also bring new features. Besides the benefits of the core/shell nanostructures, more complex nanostructures with two or more shells are developed [73; 74; 75]. The methods of synthesis of nanoparticles were classified into two general categories, depending on the size of the precursors and their evolution. According to the used approaches, a bottom-up and a top-down approach of synthesis can be defined (Figure 1) [76]. The top-down technique requires resizing big particles into smaller particles, involving etching, grinding, and cutting techniques to shape them [77]. The bottom-up process starts from smaller units to obtain a larger one using the properties that smaller units have, only generating the desired size and form. Also, the bottom-up technique can be used to produce metal and metal oxide nanoparticles with proper size and shape which could bring great interest in desired applications [78; 79; 80]. In this way, only by adding an atom to an atom can the particle be formed into preferred sizes [77]. In continuation, Figure 1 describes some examples of the most used techniques, which include chemical vapour deposition [81; 82], film deposition [83; 84], laser pyrolysis [85; 86], and others [87]. In the case of top-down approaches, the methods are different and involve mechanical techniques, laser beam processing [88; 89], and lithography [6; 90]. It was concluded that the synthesis of core/shell nanoparticles requires, especially, a bottom-up approach where the shell is built onto the magnetic core. To assist the synthesis of the core@shell structures and to control their characteristics, the method for preparing the core of nanoparticles can be either a top-down or a bottom-up approach; however, usually, the shell is obtained through a bottom-up approach, being more convenient for developing uniform coatings for the shell material over the core nanoparticles [4]. Through the top-down approach, significant crystallographic imperfections on the surface structure are developed, which is the major limitation of this method. Depending on the device design and fabrication, these limitations might conduct in supplementary manufacturing challenges. In comparison with the top-down approach, the bottom-up approach has gained attention regarding its low cost and other advantages, such as preferential control  
Figure 1: Nanoparticle’s synthesis methods. over the manufacturing process, precision and low energy loss, and, most importantly, the formation of a smaller particle size [4]. Therefore, depending on the synthesis methods, the methods in which core@shell nanoparticles are manufactured are divided into two types: (1) in situ synthesis followed up by coating the shell material coating [91; 92; 93]; (2) core@shell formation through different methods [94; 95; 96].