Developing nanoparticles as contrast agents for cell labelling and multimodal bioimaging

• Main Author: Fragueiro, Oihane
• Other Authors: Brust, Mathias
• Published: University of Liverpool 2018
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.762833

Emergence of new bioimaging technologies requires the development of the most appropriate contrast agents for each application. In this thesis, we present the development of gold nanorods (GNRs) and chromium doped zinc gallium oxide (ZGO:Cr) for labelling mesenchymal stem cells (MSCs), which enabled multimodal in vivo monitoring of cells. GNRs are excellent contrast agents for Multispectral Optoacoustic Tomography (MSOT) due to the high absorbance of their longitudinal surface plasmon resonance (LSPR) in the Near Infrared (NIR) region of the electromagnetic spectrum. Persistent luminescent nanoparticles such as ZGO:Cr have arisen as promising optical in vivo probes due to their long emission lifetime, in the order of minutes. First, NPs were synthesised and their surface was modified to improve colloidal stability, biocompatibility and cell uptake. GNRs were prepared by the seed-mediated growth method, and modified via ligand exchange using a small thiolated PEG with a carboxylic acid terminal group. For ZGO:Cr a hydrothermal approach was followed and surface was modified with DMSA. Interactions with cells and how these interactions affect the optical properties of the nanoprobes have been also studied here. To follow a multimodal imaging approach, MSC cells were co-incubated with PEG-COOH-GNRs and DMSA-ZGO. Imaging by means of MSOT and optical imaging was conducted after subcutaneous injection, and also after intracardiac administration of labelled cells. The combination of different imaging modalities is frequently required to overcome limitations of a particular technique. In our case, MSOT offered great resolution deep into the body, enabling sub-organ localisation of labelled cells, which is not possible with pure optical-based techniques. However, organs such as lungs and stomach cannot be visualised and endogenous absorbers with similar optical spectrum than GNRs could lead to false positives. On the other side, persistent luminescence did not present those limitations, however its spatial resolution is much worse than MSOT. Therefore, the two imaging modalities complemented each other to have a more accurate view of the process.