Precision imaging and nanoimmunotherapy for inflammatory atherosclerosis

Atherosclerosis is the key underlying mechanism of many cardiovascular diseases that eventually may lead to clinical events such as stroke, myocardial infarction and peripheral artery disease. Insights in vascular immunology have shifted the field’s focus from considering atherosclerosis primarily a lipid driven disease to an inflammation mediated disorder. The overarching goal of the work described in this thesis is to lay the groundwork for next generation of atherosclerosis management focusing on monitoring and controlling the innate immune response.
First I provide a perspective on how the synergistic power of PET/MR imaging can aid in unraveling the impact different comorbidities can have on the hematopoietic system and atherosclerosis progression. Next, I present different multimodal imaging protocols, facilitated by radiolabeled nanobodies and partial antibodies allowing atherosclerotic plaque phenotyping. Afterwards, two new radiotracers are presented to noninvasively study macrophage dynamics in the context of atherosclerosis. The imaging section of this thesis is concluded by a novel fluorine based nanoprobe, applied for in vivo labeling of myeloid cells that can be tracked over time to study inflammation dynamics in atherosclerotic mice after myocardial infarction by multimodality imaging.
In the second part of this thesis, a short introduction on different concepts of nanoimmunotherapeutics is provided. Subsequently, I discuss the impact of different nanocarrier platforms, followed by an evaluation of a hyaluronan-based and a HDL-based nanoimmmunotherapeutic that both showed reduced plaque inflammation in atherosclerosis models. Finally, a strategy to scale up nanoimmunotherapy production is integrated with an imaging-guided evaluation as an intermediate step towards clinical translation.