Preparation and characterization of three-layer, isotopically labelled core-shell nanoparticles; a tool for understanding mechanisms of bioavailability

- We have successfully synthesized isotopically labeled three layered core-shell nanoparticles
- The synthesis method has been shown to be reproducible and adaptable to create a range of nanoparticle sizes and layer thicknesses
- Dissolution data has shown that the isotope labelling allows for the distinction between particulate and ionic fractions
- The nanoparticles are available to quantify the respective bioavailability of the particle and the ion (from dissolution).

This paper reports the synthesis of three-layered, isotopically labelled 109Ag@Au@107Ag nanoparticles (NPs). It is proposed that this tool will be better able to fully quantify the relative importance of NP and ion (from NP dissolution) biouptake in future studies. A three-step hydrothermal synthesis procedure was developed. The final product had a middle Au barrier layer which was sufficiently thick to prevent the dissolution of the mono-isotopic (109Ag) core, despite the possibility of some alloying at the boundaries between Ag and Au. In addition, the 107Ag shell needed to be sufficiently thick to prevent complete dissolution over a relevant biological exposure period to prevent effects of the alloy on the bioaccumulation. In order to be fit for purpose, there must be good control of NP properties such as size and capping agent. After synthesis, a multi-method approach was used including scanning transmission electron microscopy (STEM), dynamic light scattering (DLS), uv-vis spectroscopy and centrifugal ultracentrifugation and inductively coupled plasma mass spectroscopy (ICP-MS) to quantify particle properties, including dissolution. The DLS, STEM and uv-vis data are strongly suggestive that a NP with three separate layers are produced, although it is acknowledged that some alloying cannot be completely ruled out. Dissolution data of the labelled NPs confirms that there is no dissolution of the Ag109 core NP or Au inner layer but partial dissolution of the Ag107 outer layer. In comparison, the dissolution data from the unlabeled NPs can only confirm the absence of dissolved Au. The middle barrier layer of Au helps prevent any hypothetical alloying affecting the particle properties as a tool to quantify dissolution impacts on bioavailability.