# Multimodal Magnetic-Plasmonic Nanoparticles for Biomedical Applications
## 2 Synthetic Methods
### Coprecipitation Techniques
#### 2.1.3 Synthesis of Magnetic-Plasmonic Nanoparticles without Intermediate Layers  
Multimodal magnetic plasmonic structures can also be synthesised by co-precipitation followed by direct attachment of the plasmonic moiety to the magnetic particles. Hydroxylamine has frequently been utilised as a seeding and reducing agent in a number of cases for coating of magnetic nanoparticles with a plasmonic shell [24; 27; 28]. For example, [PERSON] et al. first synthesised ultra-small Fe\({}_{3}\)O\({}_{4}\) NPs using [PERSON]'s coprecipitation; then, hydroxylamine was used as a seeding agent for the gold NPs (Figure 2) [28].  
Self-organising silver and ultra-small iron oxide nanoparticles were recently made using a green synthetic approach [29]. The coprecipitation method was slightly modified in this case--ginger rhizome extract was used as a stabilising agent, as well as serving as an antioxidant to prevent oxidation of the Fe\({}^{2+}\) ions. To the iron salts and ginger route extract, silver nitrate was added dropwise, followed by NaOH, and the resultant mixture was heated under reflux. The entire process takes place exclusively in aqueous solution, with magnetic separation utilised to clean and purify the Ag-Fe\({}_{3}\)O\({}_{4}\) nanocomposite product (Figure 3).  
The synthesis of magnetic plasmonic nanostructures with non-platonic geometries is a growing area of interest within this field, as these novel structures have a large surface area, strong NIR (Near Infrared) absorbance, plasmonic hot spots and interesting interactions with cells and cell components [30; 31; 32]. For example, an Fe\({}_{3}\)O\({}_{4}\) inner core was coated by a smooth layer of gold which then acted as a basis for the growth of the gold spikes to produce star-like Fe\({}_{3}\)O\({}_{4}\)@Au magneto-plasmonic supraparticles (Figure 4) [33]. Variation in the redox potential of the gold reducing agent is used to vary the morphology of the gold layer--the smooth layer of gold on the surface of the Fe\({}_{3}\)O\({}_{4}\) nanoparticle is grown through introducing the pre-formed citrate stabilised Fe\({}_{3}\)O\({}_{4}\) NPs into the boiling HAuCl\({}_{4}\) solution (citrate acts as both the stabilising and the reducing agent in this case). Hydroquinone is then used as the reducing agent in the formation of the gold spikes, as it has a more negative redox potential than citrate [33].  
Figure 2: A scheme of the synthetic approach utilised (**a**–**d**) to obtain first ultra-small magnetite (USM) nanoparticles, followed by addition of gold to form Fe\({}_{3}\)O\({}_{4}\)@Au nanoparticles, and lastly the formation of the composites using either citrate or tiopronin as a reducing agent, and purification using magnetic separation. Reprinted with permission from [28]. Copyright The Royal Society Publishing, 2016.  
Figure 4: TEM (transmission electron microscopy) images illustrating the size dependence of the supramolecular spiky nanostructures on the amount of smooth Fe\({}_{3}\)O\({}_{4}\)@Au seeds initially introduced (**a**) 4.5 nM; (**b**) 8.9 nM; (**c**) 13.2 nM; (**d**) 17.5 nM. Reprinted with permission from [33]. Copyright WILEY-VCH, 2013.  
Figure 3: High resolution TEM images showing the Ag-Fe\({}_{3}\)O\({}_{4}\) nanocomposites, and elemental mapping illustrating the location of the silver and iron oxide. Reprinted with permission from [29]. Copyright Elsevier, 2017.