Exploration and application of nanomedicine in atherosclerotic disease

In this thesis the potential of nanomedicine to treat atherosclerotic disease is examined. The research presented addresses the development and characterization of various nanodrugs, nanoparticle targeting concepts in atherosclerotic disease, as well as the use of noninvasive imaging to characterize therapeutic efficacy of new atherosclerosis therapeutics. The thesis consist of three parts, with the first part focusing on a natural nanoparticle, high-density lipoprotein (HDL). Development, characterization and application of an HDL nanoparticle to specifically inhibit atherosclerotic plaque inflammation are shown. The second part of this thesis is centered on long-circulating nanoparticles. Methods to non-invasively image atherosclerosis are developed, as well as methods to produce liposomal nanoparticles according to good manufacturing practice (GMP). The third part is focused on the use of liposomal nanoparticles to reduce inflammation in atherosclerosis. The anti-inflammatory drugs, glucocorticoids, are encapsulated in liposomal nanoparticles and their therapeutic efficacy is assessed by noninvasive multimodal imaging in a model of atherosclerosis. Consequently GMP production is commenced, and therapeutic efficacy of the nanoparticles is assessed. Afterwards a clinical trial is reported, in which delivery and therapeutic efficacy of liposomal nanoparticles is evaluated in patients with atherosclerosis. Nanomedicine holds promise as a type of personalized medicine for the management of cardiovascular disease in general, particularly the target-specific treatment and imaging of atherosclerotic disease. The continuous discovery of new molecular targets, improved understanding of the pathophysiology of atherosclerosis, as well as developments in nanoparticle synthesis methods and imaging technologies will aid in the prevention and treatment of this disease.