# Magnetic Nanomaterials for Magnetically-Aided Drug Delivery and Hyperthermia
## 11 Magnetic Nanoparticles in Preclinical Studies  
There are two main factors that need to be considered when MNPs are used in clinical settings: biological challenges and chemical challenges [97]. Biodistribution of MNPs, biological barriers and pharmacokinetics are a few biological challenges [97]. Chemical challenges include optimizing physicochemical properties, intrinsic toxicities, and drug loading and release. Further, MNPs should be biologically inert and should be composed of biodegradable and  
Figure 8: The change in coercivity of magnetic particles as a function of size. r\({}_{\rm c}\): critical parameter, r\({}_{\rm sp}\): threshold radius for superparamagnetism. With permission from [PERSON]; [PERSON], Magnetism in Nanomaterials: Heat and Force from Colloidal Magnetic Particles. In Magnetic Nanomaterials: Applications in Catalysis and Life Sciences, [PERSON]; [PERSON], Eds. Royal Society of Chemistry: London/UK, 2017; Vol. 26, 1–21. Copyright Royal Society of Chemistry, 2017.  
non-toxic materials [97]. Most of the research groups have used Fe\({}_{3}\)O\({}_{4}\) or \(\gamma\)-Fe\({}_{2}\)O\({}_{3}\) coated with different materials for clinical purposes [35]. Iron-oxide nanoparticles doped with Gd(III) has been used to treat tumors via magnetic fluid hyperthermia (MFH). [PERSON] and co-workers have found that the mouse models treated with Gd\({}_{0.02}\)Fe\({}_{2.98}\)O\({}_{4}\) show slower tumor growth after the first treatment cycle [98]. [PERSON] and co-workers synthesized Mn-Zn ferrite MNCs coated with PEG-phospholipids (1,2-distearoyl-\(sn\)-glycero-3-phosphoethanolamine-\(N\)-methoxy(polyethylene glycol) copolymers, DSPE-PEG2000) to treat tumors, and they were able to use them to induce the apoptosis of tumor cells and inhibit the angiogenesis of tumor vessels. This enables the suppression of tumor growth within a certain period of time [99]. [PERSON] and co-workers have developed versatile nanocomposite nanoparticles by decorating the surface of mesoporous silica nanoparticles with magnetite nanocrystals. These nanoparticles were able to be used in magnetic resonance (MR) imaging (Figure 9). The authors found that doxorubicin (DOX), which is an anticancer drug, can be loaded in the pores of the nanoparticles and induce cell death. In-vivo passive targeting and nanoparticle accumulation at tumor sites were confirmed using T2 magnetic resonance imaging and fluorescence imaging [100]. In order to monitor if DOX was successfully delivered to the tumor sites, tumor tissue of mice treated with DOX was analyzed and compared to a control group. Apoptosis was detected in treated tissue by means of a TUNEL assay (Terminal deoxynucleotidyl transferase-mediated nick end labeling). This confirmed the delivery of the anticancer drug to the tumor sites, and that its activity was retained during the process (Figure 10) [100]. Figure 9: “Uniform mesoporous dye-doped silica nanoparticles immobilized with multiple magnetite nanocrystals on the surface (designated as Fe\({}_{3}\)O\({}_{4}\)-MSN)” [100]: (**a**) cartoon of the nanoplatform, (**b**) TEM images of the carrier MSN, (**c**) TEM image of the Fe\({}_{3}\)O\({}_{4}\)-MSN, with permission from [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; [PERSON]; Uniform mesoporous dye-doped silica nanoparticles decorated with multiple magnetite nanocrystals for simultaneous enhanced magnetic resonance imaging, fluorescence imaging, and drug delivery. _JACS_**2009**, _132_ (2), 552–557. Copyright American Chemical Society 2009. [PERSON] and co-workers have developed a multifunctional system in order to deliver drugs intracellularly, while they monitor this process with simultaneous fluorescent imaging. This system is composed of histidine-tagged, cyan fluorescent protein (CFP)-capped, magnetic mesoporous silica nanoparticles (MMSNs). As often found with mesoporous silica nanoparticles, this multifunctional nanostructure is excellently biocompatible.