## 4 Applications of Fe\({}_{3}\)O\({}_{4}\) Nanoparticles
### Biomedical Applications (Therapeutic and Diagnostic Technologies)
#### 4.1.2 Magnetic Hyperthermia  
Magnetic hyperthermia has been documented as a promising therapeutic approach in cancer treatment. During these treatments, magnetic NPs provide heat to kill tumor cells in the presence of an alternating current (AC) magnetic field [34,111]. Tumor cells are destroyed upon the application of heat at 43 \({}^{\circ}\)C to 46 \({}^{\circ}\)C for a particular duration, while healthy cells are less affected by these treatments [112,113]. For safe clinical requirements, the product of the AC field amplitude and frequency should be smaller than \(5\times 10^{9}\) Am\({}^{-1}\) s\({}^{-1}\)[114]. Hence, Fe\({}_{3}\)O\({}_{4}\) nanoparticles must meet two criteria to be utilized as an efficient hyperthermal agent. First, they should achieve high heating efficiency under the safe range of the AC field with a small dose of MNPs. Second, nanoparticles should form stable colloids that allow intravenous injection or delivery to tumors via the bloodstream. In addition, Fe\({}_{3}\)O\({}_{4}\) NPs should be functionalized to enhance biocompatibility and colloidal stability or conjugated with recognition molecules for specific target molecules. Superparamagnetic NPs potentially represent a good candidate because they exhibit good dispersion and a lack of aggregation due to their negligible coercivity values and remnant magnetization. In contrast, SPM NPs can suffer from low heating power and require a high dose of materials due to low saturation magnetization. Although ferrimagnetic NPs exhibit high heating efficiency, stable colloids of these NPs are difficult to prepare due to the strong magnetic dipole interactions of ferromagnetic particles. The mechanism of heat generation is governed by the hysteresis loss mechanism for ferro- and ferrimagnetic NPs [35]. Meanwhile, Neel and Brown relaxations are the main heating mechanisms for superparamagnetic NPs. The specific absorption rate (SAR), also called the specific loss  
Figure 8: **(a)** TEM image of 22 nm nanocubes encapsulating PEG-phospholipid. **(b)** Image of colloidal iron oxide nanocubes. In vivo MR images of the tumor site: **(c)** without colloid injection and **(d)** after 1 h (intravenous injection). MR contrast effect of ferrimagnetic iron oxide nanocubes with different sizes: **(e)** T\({}_{2}\)-weighted MR images obtained with various concentrations of iron in a 3 T field and **(f)** their color-coded presentation. Reproduced with permission from ref. [106]. Copyright 2012 American Chemical Society. power (SLP), is measured by calculating the rate of absorbed energy per unit of mass in W/g to evaluate the heating efficiency of NPs. Numerous studies have investigated the effects of the size, geometry, and anisotropic properties of magnetite NPs on their hyperthermia performance under different AC magnetic field conditions. In one study, 26 nm Fe\({}_{3}\)O\({}_{4}\) spheres (diameter) and cubes (edge) prepared using solvothermal methods exhibited a much higher SAR value, especially when increasing the magnetic field amplitude [71]. A more comprehensive study of the effects of the Fe\({}_{3}\)O\({}_{4}\) nanocrystal sizes and geometries on heating efficiency was conducted by [PERSON] et al. [41]. Spherical and cubic Fe\({}_{3}\)O\({}_{4}\) NPs with sizes ranging from 10 to 100 nm were synthesized, and their heating efficiency was evaluated. At 800 Oe and 310 kHz, the optimum sizes of nanospheres for hyperthermia range from 30 to 50 nm (650 W/g), and nanocubes with sizes ranging from 30 to 35 nm are better heaters. Furthermore, the study suggested that nanocubes supply more heat than nanospheres with a size smaller than 35 nm, while nanospheres with a size larger than 35 nm are better heating agents. The hyperthermia performance of Fe\({}_{3}\)O\({}_{4}\) nanocubes with sizes ranging from 13 to 40 nm was recorded at different magnetic field amplitudes from 2.3 to 30 kAm\({}^{-1}\), with three different frequencies of 320, 520, and 720 kHz [52].