The project started successfully but experienced very soon considerable delays due to the COVID-19 pandemic. Recruitment of staff was delayed due to travel restrictions. Research could initially not at all be performed due to measures to work from home, limited access to lab space, and worldwide problems in availability of lab consumables. Fortunately, the ESRs have now fully started, however some with a delay, and for all problems solutions have been found that comply with the aims of the project.
The ESRs 1 -5, 15 have focused on the synthesis, preparation, and characterization of nanomaterials that have multifunctional capabilities. This means that the design of the NPs could incorporate different features like other contrast/imaging components (ESR5), coatings like PEG to control toxicological and pharmacological parameters (ESR2 and ESR5), delivery components for sustainable release of therapeutic payloads or functional linkages to other molecules for targeted delivery at specific sited like peptides targeted at CD11b (ESR4) or at cardiac stromal cells (ESR3). Primary application was of course the compatibility of PFC with 19F MRI and has been investigated by the ESRs 1-5. ESR15 worked on the design of a successful method to introduce a fluorinated probe into an antibody fragment and the consequent biological assays and imaging on neoplastic cells.
ESRs 10, 11, and 13 have worked on the development of multimodality probes for optical and MR imaging. Dual-modal imaging probes would be beneficial for both cell fluorescence imaging and in vivo 19F MRI with high sensitivity and deep penetration in tissue. 19F MRI contrast agents in the form on PFC nanoparticles and NEs will be formulated together with a near infrared fluorescent (NIRF) dye so that detailed information regarding deep tissues and cell localization can be obtained simultaneously. ESR11 initiated efforts on the development of a new fluorophore system for carbon monoxide (CO) sensing in vivo by incorporating NIR dyes in NPs. ESR13 analysed cytokine/chemokine markers of macrophage polarisation and tested different chemical materials to induce macrophage phenotypes.
Tracking fate and function of specific cell types by molecular imaging methods is of great importance for basic research and holds the potential to be clinically applied for initial diagnosis as well as the monitoring of subsequent pharmacological treatment. ESRs 6, 7, 8, 9, 12, 14 and 15 are working on the development of novel 19F MRI applications relevant for clinical translation. These include 19F MRI angiography of venous and arterial structures, myocardial perfusion (ESR 6), inflammation (immune cell trafficking (ESR 7), macrophages), and structural/functional cardiac imaging in ischemic heart disease, thromboembolism and chronic thromboembolic pulmonary hypertension (ESR 8). A further application will involve monitoring of DCs (ESR9) or cancer immunotherapy.
