## 4 Applications of Fe\({}_{3}\)O\({}_{4}\) Nanoparticles
### Biomedical Applications (Therapeutic and Diagnostic Technologies)
#### 4.1.2 Magnetic Hyperthermia
The 19 nm cubes show the highest SAR values at all frequencies, which can reach 2452 W/g at 520 kHz and 29 kAm\({}^{-1}\). Additionally, studies of the magnetic properties showed that 19 nm nanocubes are located at the transition point from superparamagnetic to ferrimagnetic, consistent with the hypothesis proposed in previous studies for the higher SAR value of iron oxide nanoparticles in this transition size range [115]. [PERSON] and coworkers also compared the heating efficiency of nanocubes with sizes of 13, 15, and 19 nm and 22 nm spherical NPs at 17 kA/m and 183 kHz and obtained the best heating efficiency for 19 nm cubic Fe\({}_{3}\)O\({}_{4}\) nanocrystals [74]. However, other measurements were conducted at different frequencies, such as 109, 220, and 300 kHz, for a similar size range (14 to 35 nm) of Fe\({}_{3}\)O\({}_{4}\) nanocubes and produced a slightly different result [44]. Nanocubes with sizes of 19 and 24 nm showed the best SAR value under most of the measured conditions and saturated at approximately 18 kAm\({}^{-1}\); however, 35 nm cubes showed higher SAR values at magnetic field amplitudes of 20-24 kAm\({}^{-1}\). [PERSON] et al. synthesized Fe\({}_{3}\)O\({}_{4}\) nanorods, nanocubes, and nanospheres with comparable volumes and determined that nanorods achieve a higher SAR value of 862 W/g, which is much higher than nanocubes (314 W/g) and nanospheres (140 W/g) [40]. Furthermore, increasing the aspect ratio of nanorods was proven to help increase the SAR value of magnetite nanorods. Thus, the heating efficiency of magnetite nanoparticles is affected by the shape and size of the nanoparticles and remarkably depends on the frequency and amplitude of the applied AC magnetic field. Functionalization of Fe\({}_{3}\)O\({}_{4}\) NPs or core-shell architectures was studied to further enhance the heating performance, biocompatibility, and stability of colloids. [PERSON] et al. synthesized chitosan oligosaccharide-coated packs of four to ten 30 nm-sized Fe\({}_{3}\)O\({}_{4}\) nanocubes and investigated the hyperthermia activity [116]. These particle cluster-coated chitosan nanoparticles exhibited a superior magnetic heating ability with a high specific loss power of 2614 W/g, which is much higher than that of commercial Feridex nanoparticles (83 W/g). Chitosan oligosaccharide was used to improve colloidal stability and blood circulation in vivo. Continuing the particle clustering strategy to enhance magnetic hyperthermia, [PERSON] et al. studied the effect of individual nanocubes, dimers or trimers (two or three nanocubes), and centrosymmetric clusters (more than four nanocubes) on SAR values [117]. TEM images of monomers, dimers, trimers, and centrosymmetric clusters are shown in Figure 9a-c. The prepared nanocubes stabilized with oleic acid were coated with the amphiphilic copolymer poly(styrene-comaleic anhydride). The degree of clustering was controlled by the ratio of polymer/surface area of nanocubes, as illustrated in Figure 9d. The SAR data shown in Figure 9e indicate that the dimers and trimers exhibit the best heating efficiency. In another study, [PERSON] et al. confined nanocubes inside submicrometer cavities to preserve magnetic heat losses in an intracellular environment [118]. Anotherstudy of 2D assemblies of magnetic nanocubes exploited enzymatic polymer disassembly to improve magnetic hyperthermia heat losses [119]. Interestingly, [PERSON] et al. utilized 20 nm Fe\({}_{3}\)O\({}_{4}\) nanocubes with a dual capacity to act as both magnetic and photothermal agents [120]. Upon exposure to an AC magnetic field and near-infrared laser irradiation, an aqueous suspension of magnetite nanocubes achieved an unprecedented heating power up to 5000 W/g. The dual mode of magnetic hyperthermia and photothermal resulted in complete apoptosis-mediated cell death and complete solid tumor regression in vivo. [PERSON] et al.