Reverse micelles are essentially formed by aqueous iron salt solutions, encapsulated by a surfactant that separates them from the surrounding organic solution. Publications have suggested that iron oxide nanoparticles synthesised via the reverse micelle process can be used for MRI applications . For example Lee et al. , investigated an inexpensive, large-scale, and highly crystalline method of magnetite production. The synthesis was carried out at high temperatures whilst varying the relative proportion of iron salts, surfactant and solvents. It was suggested that the particle size could be controlled to produce monodisperse particles in one sample.
There are many studies on the synthesis of SPIONS using the high temperature method, for example Sun and Zeng  prepared iron oxide nanoparticles of different sizes, 3nm to 20nm. In this reaction, iron(III) acetylacetonate was decomposed by heating at 265oC in phenyl ether, alcohol, oleic acid, and oleylamine, to produce SPIONS 4nm in diameter. To make larger particles, a seed-mediated growth was used, controlling the quantity of seeds added to obtain various sizes.
The research on superparamagnetic iron oxide nanoparticles (SPIONs) has been growing exponentially over the last several years. The field continues to drive in the direction of biomedical applications, especially molecular therapeutics by exploiting the immense qualities of SPIONs . This includes the distinctive controllable properties such as size, shape, magnetism, crystallinity and flexibility in fabricating multifunctional SPIONs with fluorescence, targeting ligands, drugs etc, thanks to the advancements in the syntheses and functionalization techniques developed hitherto. There are some excellent synthetic methods in prior arts on the formation of superparamagnetic magnetite (Fe3O4) and maghemite (γ-Fe2O3) SPIONs, with size control, narrow distribution, water solubility and surface functionalization [-]. The co-precipitation method is a conventional synthetic paradigm where Fe(II) and Fe(III) salts are co-precipitated in a basic solution in the presence of coating materials such as polymer or dextran (or its derivatives). Although the resulted iron oxide nanoparticles (NPs) are larger in size (ca. 100 nm) and partially crystalline, the particles are readily water soluble where their surfaces are directly functionalized. Alternatively, thermal decomposition method using precursors such as Fe(CO)5, Fe(Stearate)2, with high boiling solvents (octadecene, benzyl ether) and surfactants/ligands (oleic acid, oleylamine) can be used to synthesize smaller sized hydrophobic SPIONs (5-10 nm). In order to impart the SPIONs with water solubility for biomedical applications, water-oil microemulsion method can be employed as a reaction medium for coating a hydrophilic ligand (e.g. silica, peptides) on the hydrophobic surface.
In another interesting work, Louie and coworkers have reported the synthesis of a reversible T2 contrast agent that is capable of modulating the relaxation time in response to light irradiation . A spiropyran (SP) derivative that changes conformation between hydrophilic and hydrophobic isomers in response to light, has been covalently attached to dextran sulfate coated iron oxide nanoparticles (ADIO). The light induced reversible aggregation of MNPs has been found to modulate the T2 relaxation time (Figure ).
Monodisperse Fe nanoparticles are synthesized via a simple one-pot thermal decomposition of Fe(CO)5 in the presence of oleylamine. Controlled oxidation of the iron surface leads to crystalline Fe3O4 shell and results in dramatic increase of chemical and dispersion stability of the nanoparticles. Surface ligand exchange is readily applied to transfer the core/shell nanoparticles from hydrophobic to hydrophilic, and a stable aqueous nanoparticle dispersion in PBS is formed. The functionalized nanoparticles are suitable for biomolecule attachment and biomedical applications.
The chemical synthesis of bimetallic nanoparticles of Pt with highly reactive non-noble solute metals offers particular synthetic difficulties . The present work investigates and identifies optimal synthesis of highly monodisperse hydrophobic Pt-Ni, Pt-Co and Pt-Fe alloy nanoparticles with fine-tuned size and uniform size distribution, shape and composition, using a single (and simple) synthetic preparation protocol. When Pt-based bimetallic nanoparticles are synthesized by the chemical co-reduction of two kinds of metal inorganic precursor salts, the degree of chemical reduction is significantly influenced by the reaction temperature and the reducing agents used. In the present work, surface active agents are employed to manipulate particle growth and direct shape evolution, stabilize the particles and limit the degree of nanoparticle oxidation. The fabrication route reported here can be an effective tool for large-scale production of metallic nanoalloys.
Platinum-based bimetallic nanoparticles in the size range 5–9 nm were successfully synthesized by the simultaneous reduction of Pt and M precursor salts in a homogeneously mixed solution of surfactants. The degree of reduction was manipulated both by temperature and by the reducing agent employed; the reaction time was 60 min in each case.
The production of multimetallic nanoparticles adds further variables to the synthesis: the nucleation and growth processes of such nanoparticles are difficult to manipulate due to the typically distinct thermodynamic and kinetic characteristics of different metals; the ultimate composition of the alloy nanoparticle is accordingly challenging to regulate . The synthesis of Pt-based alloy nanoparticles with highly reactive solutes such as Ni, Co and Fe thus offers particular difficulties in preparation: because of a large difference in the driving mechanism for reduction of the Pt and M precursors, simultaneous reduction may be elusive. In order to circumvent this, the nucleation and growth stages must be well controlled to provide feedstock for stable Ostwald ripening and also to avoid the spontaneous formation of separate Pt and M monometallic nanoparticles.
5. Ge S, Shi X, Sun K, Li C, Uher C, Baker JR, Banaszak MM, Orr BG. Facile hydrothermal synthesis of iron oxide nanoparticles with tunable magnetic properties. 2009;113:13593-99
In the present work, we introduced a strong reducing agent (TBAB) and high temperatures together with a high-boiling-point solvent (BE), to accelerate the reduction of the solute-metal salts and thus to ensure that the kinetics of the reduction of Pt and M precursors are similar. The solvent BE was chosen in this synthetic strategy in order to provide a medium for complete nucleation, growth and interatomic diffusion of both types of metallic atom. A mixture of stabilizing agents, such as OAm, TOA, ODA and OA was used during synthesis in order to regulate the size, dispersion and provide anisotropic growth of alloy nanoparticles. As illustrated in , the synthesis of alloyed nanoparticles in solution-phase by the co-reduction of different metal precursors ideally results in an ordered or disordered arrangement of the different atoms in each nanoparticle, rather than separate nanoparticles of each metal. Our wet chemistry synthetic strategy takes into consideration all the critical reaction parameters for the uniform size and bimetallic compositional control of nanoparticles. Thus, in our preparation route of choice for the synthesis of alloy nanoparticles; the nucleation, growth process and composition of bimetallic nanoparticles were controlled by regulating reaction parameters such as the molar ratio between metal precursors and surface active agents (surfactants), the reaction temperature and time, and reducing agents.
Different bimetallic nanoparticles of Pt-Ni, Pt-Co and Pt-Fe were accordingly synthesized by the single simultaneous reduction of Pt and M metal precursor salts in the presence of surfactants such as OAm, TOA, ODA or OA with TBAB; at 220 °C for Pt-Ni and Pt-Co, and at 260 °C for Pt-Fe; in high-boiling point solvent BE. The higher temperature used for Pt-Fe shortened the reaction time from two hours (at 220 °C) to one hour, consistent with the reaction time of Pt-Ni and Pt-Co. The reduction of both metal ions appeared to be complete after 60 min of heating for all mixtures, forming a dark-brown colloidal solution. This high-temperature reduction route yielded highly monodisperse bimetallic nanoparticles less than 10 nm in size.
In recent years, multifunctional nanoparticles (NPs) consisting of either metal (e.g. Au), or magnetic NP (e.g. iron oxide) with other fluorescent components such as quantum dots (QDs) or organic dyes have been emerging as versatile candidate systems for cancer diagnosis, therapy, and macromolecule delivery such as micro ribonucleic acid (microRNA). This review intends to highlight the recent advances in the synthesis and application of multifunctional NPs (mainly iron oxide) in theranostics, an area used to combine therapeutics and diagnostics. The recent applications of NPs in miRNA delivery are also reviewed.