To achieve project’s goals, initially, we have optimized the synthesis of individual nanoparticles, i.e. silica coated gold nanorods having different aspect ratios, luminescent nanoparticles, and superparamagnetic iron oxide nanoparticles (SPIONs). These particles were tested for their characteristics including imaging potential and their effect on cells’ viability was evaluated. Later, polyelectrolyte multi-layered and multifunctional capsules were fabricated which were incorporating nanoparticle-based imaging probes as individual particles and also in combination in defined ratio inside single particle for bio-luminescence (luminescent nanoparticles), magnetic resonance (SPIONs), and multispectral optoacoustic tomography (MSOT; gold nanorods) having desired properties (sharp intense IR absorbance, high luminescence and magnetic susceptibility). Phantoms mimicking the biological tissues containing these multimodal capsules were tested by bioluminescence, MRI and MSOT. These probes retained their unique imaging characteristics after incorporation inside single entity (capsules). It was also possible to incorporate two types of gold nanorods having different dimensions (aspect ratios) inside single capsule which retained their characteristic IR absorbance properties and had potential applications in enhancing the sensitivity of detection of MSOT through engineering of an ideal spectrum (work in progress). These multimodal imaging probes were tested for their cellular uptake, accumulation, labelling efficiency and effects on cell phenotype using a range of in vitro assays in mouse bone marrow derived mesenchymal stem cells (mMSCs). The probes tailored by this approach showed significant potential for multimodal imaging when tested inside agar based phantoms and were non-toxic to the stem cells when phagocytosed with no alteration in cell phenotype. However, it was difficult to trace labelled cells in vivo because sensitivity of the detection limit for in vivo imaging and tracking depends on the amount of imaging material incorporated inside the capsules and during cell labelling the amount of imaging material taken up by the cells was below the detection limit of these imaging instruments. Therefore, for in vivo imaging and tracking the stem cells a bimodal imaging system MRI/BLI was used (genetically modified cells for producing bioluminescence signals upon stimulation labelled with superparamagnetic iron oxide nanoparticles) and it was possible to track stem cells in vivo and see the in vivo fate of the particles after cell death. Details can be found in our recent preprint (
https://www.biorxiv.org/content/early/2018/07/20/366518.article-info(se abrirá en una nueva ventana)) coupled with MR data (
https://zenodo.org/record/1203991#.W1R51dJKjIU(se abrirá en una nueva ventana)) which is submitted in Nanoscale Advances.
In addition, we have worked to optimize the synthesis of gold nanoparticles and their functionalization with peptide self-assembled monolayers (SAMS) which is helpful for their use in biological applications, such as cell tracking.
In collaborative projects we have provided silica coated gold nanorods: (1) to be initially tested in animal models (breast and pancreas) and later on in pancreatic cancer, and in the long run to look at metastatic foci (work with Chris Madsen, Sweden) (2) and to track gold nanorods labelled macrophages inside different body organs of mice by MSOT (work in the University of Liverpool).
Throughout the length of the project, the researcher has acquired extensive training in multidisciplinary fields, which included intense training in animal handling and surgical procedures (obtained personal licence from the British Home office), in vivo and in vitro imaging, and stem cell biology. This training is very useful to bridge the gap between research and the market and comes under the remit of the future objectives of the EU listed in the Horizon 2020 programme.
During the course of fellowship, the researcher was engaged in the in activities to share the research results with academics and general public via seminar presentations, scientific discussions, mentoring students, writing blog posts (
https://raphazlab.wordpress.com/tag/sumaira-ashraf/(se abrirá en una nueva ventana)) and meet the scientist events (
https://blogandlog.wordpress.com/2018/04/27/meet-the-scientists/(se abrirá en una nueva ventana);
https://blogandlog.wordpress.com/2016/12/(se abrirá en una nueva ventana)).
