# Multimodal Magnetic-Plasmonic Nanoparticles for Biomedical Applications
## 2 Synthetic Methods
### Coprecipitation Techniques
#### 2.1.2. Synthesis of Core/Polymer/Shell Magnetic-Plasmonic Nanoparticles  
Conductive polymers have been used to aid the fabrication of magnetic plasmonic nanocomposites. This approach was demonstrated by [PERSON] et al., who prepared polypyrrole encapsulated gold nanorods decorated with Fe\({}_{3}\)O\({}_{4}\) nanoparticles (Au NR@PPY@Fe\({}_{3}\)O\({}_{4}\)) [21]. Polypyrrole (PPY) is a conductive polymer that has been demonstrated to induce photothermal effects, and is already widely used in many biomedical applications [22; 23]. The core gold nanorods were synthesised using a modified seed mediated approach in which gold seeds synthesised using NaBH\({}_{4}\) and chloroauxtic acid in CTAB (hexadecyltrimethylammonium bromide), and a growth solution of AgNO\({}_{3}\), HAuCl\({}_{4}\) and ascorbic acid. Iron cation mediated polymerisation was used to fabricate the PPY coating on the gold nanorods--this gave rise to an abundance of Fe\({}^{3+}\) and Fe\({}^{2+}\) ions in the resulting PPY@Au nanorod product. This solution was then diluted with water and ethanol and the Fe\({}_{3}\)O\({}_{4}\) nanoparticles were precipitated directly out of this solution using ammonia, and adhesion of the Fe\({}_{3}\)O\({}_{4}\) nanoparticles was driven electrostatically to the conductive polymer shell.  
Aqueous based syntheses are of increasing interest, and of particular importance when the material is being considered for biomedical applications. Eliminating the use of organic solvents throughout the synthetic process and using only biocompatible, non-toxic materials and reagents streamlines the synthesis for biological purposes. An aqueous synthetic method and biocompatible polymer was utilised in the synthesis of heterostructured Fe\({}_{3}\)O\({}_{4}\)@PVP@Au nanocomposites [24]. In this synthesis, PVP (polyvinylpyrrolidone) polymer was used to stabilise the Fe\({}_{3}\)O\({}_{4}\) nanoparticles, and also to form a homogenous layer surrounding them that has a negative charge. PVP is amphiphilic, non-toxic and non-ionic and already has a broad spectrum of biomedical applications [25]. Gold seeds were prepared through the reduction of chloroauric acid using NaBH\({}_{4}\) in the presence of CTAB, and these seeds assemble on the PVP-coated Fe\({}_{3}\)O\({}_{4}\) through electrostatic interaction. The outer gold shells were formed through the use of hydroxylamine hydrochloride. Polyethyleneimine (PEI) can also be used as a reducing agent to cause the formation of an outer plasmonic layer. Fe\({}_{3}\)O\({}_{4}\)@Au structures were synthesised by [PERSON] et al.; coprecipitated Fe\({}_{3}\)O\({}_{4}\) nanoparticles were dispersed in chloroauric acid solution and placed in a shaking incubator to allow the adsorption of Au\({}^{3+}\) onto the surface of the Fe\({}_{3}\)O\({}_{4}\) nanoparticles. PEI was then added to the shaking mixture to reduce the gold, causing the formation of a gold shell on the Fe\({}_{3}\)O\({}_{4}\) nanoparticles [26]. Hydroxylamine was utilised by [PERSON] et al. in the preparation of their multimodal magnetic plasmonic Fe\({}_{3}\)O\({}_{4}\)@Au nanoparticles [27]. They first modified their Fe\({}_{3}\)O\({}_{4}\) nanoparticles with chitosan, post synthesis and stabilisation with oleic acid.  
Figure 1: A diagram illustrating the structure of the Fe\({}_{3}\)O\({}_{4}\)@Au nanoparticles. Reprinted with permission from [20]. Copyright [PERSON], 2010.  
Acetic acid is then added to the Fe\({}_{3}\)O\({}_{4}\)-Chitosan NPs and the mixture is sonicated, any unreacted chitosan is then removed using magnetic separation. Preformed gold colloids are then introduced to these particles and sonicated, and hydroxylamine hydrochloride is used to reduce the gold colloids on the surface of the Fe\({}_{3}\)O\({}_{4}\) to form a gold shell. Magnetic separation is then utilised to ensure no unreacted gold remains in the solution.