octadecene were slowly heated to a certain temperature and aged, generating monodisperse iron oxide nanocrystals. By thermal decomposition of iron oleate in the presence of sodium oleate, Zhou et al. synthesized iron oxide nanostructures with various shapes. By tuning the molar ratio of sodium oleate/iron oleate or the reaction temperature, they could obtain plates, tetrahedrons, octahedrons, concaves, multibranches and self-assembled structures (Figure 1B-C, E-G, I). This also opened up a new strategy for the controlled synthesis of other metal oxide nanoparticles. Additionally, nanocubic IONPs (Figure 1D) were synthesized by thermal decomposition of iron oleate precursors in the presence of sodium oleate as a stabilizer. By careful adjustment of the oleic acid salts as well as the reaction temperature, a series of size- and shape-controlled cubic iron oxide nanocrystals could be obtained. Zhao et al. synthesized Octapod IONPs (Figure 1H) via decomposition of iron oleate in 1-octadecene solvent containing oleic acid as the surfactant and sodium chloride.
Example morphologies of 0-dimensional IONPs: (A) nanospheres, (B) plates, (C) tetrahedrons, (D) cubes, (E) truncated octahedrons, (F) octahedrons, (G) concaves, (H) Octapods, and (I) multibranches. (A) Reproduced with permission from, copyright 2004. (B-C, E, G, I) Reproduced with permission from, copyright 2015. (D) Reproduced with permission from, copyright 2007. (F) Reproduced with permission from, copyright 2010. (H) Reproduced with permission from, copyright 2013.
In addition to the synthesis of 0-dimensional IONPs (nanoparticles), efforts have also been applied to the development of 1-dimensional and 3-dimensional structures (Figure 2). He et al. successfully obtained uniform, ultra-thin, single-crystal Fe3O4 (Figure 2A) based on a facile, surfactant-assisted hydrothermal route with the assistance of polyethylene glycol 400 (PEG-400). The as-synthesized products were nanowires with a growth direction along the  crystal direction, with a narrow diameter distribution centered at 15 nm and a length of up to several micrometers. Liu et al. firstly reported the synthesis of homogeneous single-crystal Fe3O4 nanotubes (Figure 2B) with controllable length, diameter, and wall thickness. By tuning the length and diameter of the MgO cores and the deposition time/rate of the shell using a wet-chemical etching method, the Fe3O4 nanotubes could be precisely controlled. Additionally, magnetic needle-like IONPs (Figure 2C) were developed via a microwave-assisted procedure, during which, microwave served as a source of energy for the formation of precursor particles with high aspect ratio and the source of heat required for the thermal decomposition. Wan et al. prepared uniform single-crystal Fe3O4 nanorods (Figure 2D) with an average diameter of 25 nm and length of 200 nm via a soft-template-assisted hydrothermal route at 120 °C for 20 h. Ethylenediamine was not only used as a base source but also as a soft template to form single-crystal Fe3O4 nanorods, and benzene was used to prevent oxidation of ferrous ion by oxygen in air. Through changing the ferrous ion source and solvent, single-crystal hematite nanotubes (Figure 2E) were developed via a facile, one-step hydrothermal treatment of a FeCl3 solution (0.02 M) in the presence of NH4H2PO4 (7.2×10-4 M) at 220 °C for 48 h. The Fe3O4 nanotubes had a single-wall tube structure with outer diameter of 90-110 nm, inner diameter of 40-80 nm, and length of 250-400 nm. Based on these results, single-crystal iron oxide tube-in-tube nanostructures (Figure 2F) were obtained in the same way. The structure was formed with a multisite dissolution process of ellipsoid precursors, which was also useful to achieve other complex single-crystal architectures. Furthermore, Liu et al. demonstrated a facile, inexpensive, and fast microwave-assisted hydrothermal (MAH) method for the large-scale and controllable synthesis of high-quality elliptical Fe3O4 nanorings (13-26 nm wall thickness, 1.2-2.0 long axis/short axis, and 48-213 nm long axis length). These Fe3O4 nanorings exhibited significant microwave absorption, strong dielectric loss, multiresonance behaviors, oscillation resonance absorption, microantenna radiation, and interference behaviors.
Example morphologies of 1-dimensional and 3-dimensional IONPs: (A) nanowires, (B) long nanotubes, (C) nanoneedles, (D) nanorods, (E) short nanotubes, (F) tube-in-tubes, and (G) nanorings. (A) Reproduced with permission from, copyright 2007. (B) Reproduced with permission from, copyright 2005. (C) Reproduced with permission from, copyright 2015. (D) Reproduced with permission from, copyright 2005. (E) Reproduced with permission from, copyright 2005. (F) Reproduced with permission from, copyright 2007. (G) Reproduced with permission from, copyright 2016.
In addition to the above-mentioned synthesis strategies for the production of the IONPs with various morphologies, recently, it has been observed that various morphologies can also be obtained from a single reaction by carefully adjusting the ratio or concentration of the reactants or the reaction parameters, including reaction temperature or time. Zhang et al. found that the amount of sodium acetate (NaAc) and the volume ratio of ethylene glycol (EG) and 1, 3-propanediamine (PDA) played an essential role in the formation of different morphologies of IONPs in their hydrothermal route. By keeping other reaction conditions constant, single-crystal IONPs with pseudo-octahedral, irregular or triangular nanoprism structures were obtained using different weights of NaAc in the fabrication (Figure 3A). Furthermore, the rough plate-like morphology transformed into smooth triangular nanoprisms (TNPs) with a few octahedral structures with increasing amount of PDA compared to EG. When the volume ratio of EG:PDA reached 35:5, all the TNPs changed into octahedral structures with a uniform size distribution. Apart from the influence of solvent, it has been revealed that variation of the concentration of the surfactant tetra-n-butylammonium bromide (TBAB) could modulate the microstructure and morphology of flower-like architectures (Figure 3B). With increasing concentration of TBAB from 30 to 150 mM, the flower-like structure consisted of petals with looser packing. When the TBAB concentration was as high as 150 mM, the morphology was composed of only the nanosheet structures, which indicated that TBAB could control the size of the nanosheets that compose the flower-like structures. Furthermore, previous studies revealed that reaction temperature and time were significant in the preparation of Fe3O4 nanocubes. As shown in Figure 3C, the shapes of the final products obtained at 220 °C for 2 h were roughly spherical without cubes and arranged in a closely packed array. However, plenty of nanocubes were observed when the temperature was increased to 240 °C. Additionally, prolonging the reaction time from 0.5 to 1 h could increase the number of nanocubes and lead to a more uniform size distribution. These results demonstrated that high temperatures or long reaction times seem to be desirable to get monodisperse Fe3O4 nanocubes.
Most of the previous work has focused on the design of IONPs with specific shapes. However, the aggregation state of IONPs, which is defined as an arrangement and organization of single-crystal Fe3O4, also plays an essential role in their applications as theranostic agents. Our previous work described the synthesis of iron oxide clusters (Figure 4A) as a MRI contrast agent via a one-pot hydrothermal method in ethylene glycol/diethylene glycol binary solvent. The above synthetic method could be extended to synthesize ferrite nanospheres with sizes from 20 to 300 nm by varying the ethylene glycol/diethylene glycol ratio. Liu et al. prepared monodisperse, hollow and core-shell magnetite (Fe3O4) spheres by a simple one-pot method based on hydrothermal treatment of FeCl3, citrate, polyacrylamide and urea (Figure 4B). The nanoparticle formation undergoes two stages: the formation of amorphous, monodisperse solid spheres and transformation of the solid spheres to hollow spheres or core-shell spheres. As carriers for targeted drug delivery, hierarchical hollow structures are excellent due to their efficient delivery of theranostic agents and magnetic targeting ability. Many methods have been successfully developed for the construction of hierarchical hollow structures (Figure 4C-D) [46, 47]. Additionally, well-defined porous Fe3O4 flower-like nanostructures were synthesized by decomposition of iron alkoxide precursors at high temperature under gas protection. Moreover, hollow structures of IONPs could themselves act as both drug carrier and therapeutic agent, indicating their attractive potential for magnetic theranostic applications.
Controlled synthesis of different shapes of IONPs via varying the reaction conditions. (A) Varying the solvent component ratio. Reproduced with permission from, copyright 2010. (B)