# Magnetic Nanomaterials for Magnetically-Aided Drug Delivery and Hyperthermia
## 2 Magnetic Nanoparticles  
During the last two decades, various strategies for synthesizing magnetic nanoparticles for drug delivery have been explored [36]. Magnetic nanoparticles consist of a core of magnetic iron oxide (magnetic [Fe\({}_{3}\)O\({}_{4}\)] or maghemite [Fe\({}_{2}\)O\({}_{3}\)]), and a shell comprised of diamagnetic material, for instance, silica, dextran or polyvinyl alcohol (PVA) [6; 37; 38; 39]. Noble metal shells (especially Au) were used to enable the attachment of functional groups and ligands via thiols [40; 41]. However, many of these core/shell systems prove to be chemically unstable, leading to gold-iron oxide alloys [42]. Magnetic nanoparticles can be synthesized by using ionic and non-ionic techniques [43]. There are numerous methods known to synthesize magnetic nanoparticles, such as mechanical milling [44], co-precipitation [45], nanoreactor/microemulsion techniques [45; 46], sonochemical processing [45; 46], sol-gel methods [47], flow injection [43], electrochemical production [48], supercritical fluid techniques [49; 50], thermal decomposition [13; 14; 15; 16; 22; 51; 52; 53; 54; 55], hydrothermal routes [45], microwave techniques [56], spray pyrolysis [45], laser pyrolysis [45], flame spray pyrolysis [45], gas phase synthesis [45], arc discharge [57], oxidation [58; 59], and microbial methods etc. [43; 45; 60]. Figure 1 shows a typical plot of resulting nanoparticle size distribution p(n) as a function of nucleation rate J(t) and reaction time (t) minus time of maximal nucleation (t\({}_{\rm m}\)), divided by the half-life time of the nucleation burst [61]. Figures 2 and 3 give examples of the diversity of obtainable nanostructures. Figure 1: “As time increases toward \(t_{m}\), the critical nucleus size decreases (black curved arrow), the nucleation rate increases (yellow manifold over nucleus size curve), and the earliest nuclei to form grow in the (n,t) plane. The nucleation rate reaches a maximum at time \(t_{m}\) and then begins to fall. The cumulative number of nuclei generated and carried along each characteristic gives the particle size distribution PSD p(n). For times after the pulse, the PSD simply travels along the characteristics with no change in shape.” n*: critical nucleus size, n: nucleus size, \(2\alpha_{\Pi}\): approximate duration of the nucleation burst [61]. With permission from [PERSON]; [PERSON]; [PERSON], Nucleation and Growth Kinetics from LaMer Burst Data. _J. Phys. Chem. A_**2017**, _121_ (40), 7511-7517, copyright American Chemical Society 2017. Figure 2: TEM images of (**A**) the as-synthesized 8 nm/2.5 nm Fe/Fe\({}_{3}\)O\({}_{4}\) NPs (inset: HRTEM) and (**B**) the 5 nm/5 nm Fe/Fe\({}_{3}\)O\({}_{4}\) NPs prepared by controlled oxidation of Fe NPs [62]. With permission from [PERSON]; [PERSON]; [PERSON]; [PERSON], Synthesis and stabilization of monodisperse Fe nanoparticles. _JACS_**2006**, _128_ (33), 10676-10677, copyright American Chemical Society, 2006. These synthesized magnetic nanoparticles can be functionalized by attaching carboxyl groups, amines, biotin, streptavidin, antibodies, etc. [64; 65]. By attaching functional groups to the magnetic nanoparticles one can change their physicochemical properties, such as solubility, reactivity, and stability (Figure 4) [64; 65]. Figure 4: Nanoparticle surface functionalization via (**A**) surfactant addition and (**B**) surfactant exchange [64]. Figure 3: **(A)** “Synthesis of core-shell–void Fe–Fe\({}_{3}\)O\({}_{4}\) and hollow Fe\({}_{3}\)O\({}_{4}\) NPs from Fe–Fe\({}_{3}\)O\({}_{4}\) NP seeds.”; **(B)** TEM images: a 13-nm Fe–Fe\({}_{3}\)O\({}_{4}\) nanoparticle seeds, (**C**) 16-nm hollow Fe\({}_{3}\)O\({}_{4}\) nanoparticles, (**D**) a single hollow Fe\({}_{3}\)O\({}_{4}\) nanoparticle, and (**E**) a superlattice array of the hollow Fe\({}_{3}\)O\({}_{4}\) nanoparticles.” [63] With permission from [PERSON]; [PERSON], Synthesis and characterization of monodisperse hollow Fe3O4 nanoparticles. _Angewandte Chemie International Edition_**2007**, _46_ (22), 4155–4158, copyright Wiley & Sons, 2007.