Targeted therapeutics in inflammatory atherosclerosis

Atherosclerosis, a chronic inflammatory vascular disease, which has been recently identified in 5000-year mummies, remains undefeated. It is the most common underlying cause of deadly cardiovascular diseases (CVD), including heart attacks, strokes, and peripheral vascular diseases. This tremendous socioeconomic burden calls for further investigation and investment to develop effective, innovative, and clinically viable interventions for the treatment of atherosclerosis. One important initiative in this direction is NanoAthero, a European Consortium that funded the research work presented in this thesis. This program aims to demonstrate the preliminary clinical feasibility of the use of nanosystems for targeted imaging and treatment of advanced atherosclerosis. The enthusiasm generated for the use of nanocarrier drug delivery systems in atherosclerosis is mainly driven by the significant progress made in the field of oncological nanomedicine. Capitalizing on the achievements in the nanomedicine field, the main aim of this thesis is to contribute to the development and use of targeted nanomedicines in atherosclerosis. To this end, we adopted a ‘disease first’ approach to develop efficient targeted nanomedicines, in which particular attention is paid to the underlying pathophysiological processes in atherosclerosis. Macrophages are key players in these processes that affect atherosclerotic plaque inflammation and vulnerability to rupture. Moreover, their phagocytic capacity makes macrophages ideal targets for nanomedicine-based approaches. Understanding the role of plaque-associated macrophages and their interactions with the different nanocarriers is crucial for the successful development of efficacious, clinically relevant nanotherapeutics for atherosclerotic cardiovascular diseases.