Diseases of the arterial wall leading to acute arterial thrombosis and cardiovascular events are predominant causes of death in developed countries and they account for considerable morbidity and mortality worldwide.
Atherosclerosis is an important arterial wall disease characterized by focal lesions with asymmetric thickenings of the innermost layer of the artery. The lesions of atherosclerosis occur principally in large and medium-sized elastic and muscular arteries and can lead to ischemia of the heart, brain, or extremities. In such arterial disorder, inflammatory cells, activated smooth muscle cells, lipids, and extracellular matrix accumulate in the arterial wall resulting in growth of plaques. In the core of an atheroma, foam cells and extracellular lipid droplets form a core region, which is surrounded by a cap of smooth-muscle cells and a collagen-rich matrix. Although advanced atherosclerotic lesions can lead to ischemic symptoms as a result of progressive narrowing of the vessel lumen, acute and severe cardiovascular events generally result from plaque rupture.
Plaque rupture is one of the leading causes of thrombosis. Blood exposure to prothrombotic material from the core of the plaque (phospholipids, tissue factor, and platelet-adhesive matrix molecules) disrupts homeostasis. When such pathologic processes overwhelm the regulatory mechanisms of homeostasis, thrombin is excessively formed, initiating thrombosis. Platelets have a central role in cardiovascular thrombosis. They adhere to the sub-endothelial matrix after endothelial damage, then aggregate with each other to form a prothrombotic surface that promotes clot formation and subsequently vascular occlusion. Thrombotic occlusion of a coronary artery results in acute myocardial infarction and thrombotic occlusion of a cerebral artery results in acute ischemic stroke.
Current strategies to fight the consequences of atherothrombosis are orientated either towards the promotion of a healthy life style (smoking suppression, balanced nutrition) and pharmacological treatment of ‘systemic’ risk factors (dyslipidemia, hypertension, hyperglycaemia), or towards late interventional strategies including device placements, thrombolysis, etc. For acute vascular events, prompt revascularization is indicated in order to save tissue. In acute stroke, revascularization by using thrombolytics immediately restores blood flow thereby limiting brain damage. However, thrombolytic therapy needs improvement for increased efficacy and decreased side effects (i.e. intracranial haemorrhage). Despite this therapeutic arsenal, the incidence of clinical events remains dramatically high. This illustrates that there are diagnostic and therapeutic gaps between non-invasive screening and prevention in one hand, and emergency invasive diagnostic and treatment on the other. Considering the severe and widespread morbi-mortality associated to atherothrombotic diseases, there is an urgent need for new approaches for early diagnosis and improved targeted therapies. This is the focus of NanoAthero via the development of effective, safe, and innovative targeting nanoparticulate systems.
Although nanoparticle-based therapy is becoming more and more common in cancerology, no specific nanoparticle-based system has yet been approved for diagnosis or therapy in cardiovascular diseases. Indeed, integrating a transport mechanism, a stealth coating, targeting and an active molecule into one and the same nanosystem (known as a third-generation nanosystem) has not yet been clinically validated in the field of atherosclerosis.
Several NanoAthero partners have patented and provided proof of the efficiency of different nanodelivery systems and ligands for use in targeted therapies. This recent progress is of major importance for the development of new molecular and therapeutic diagnosis tools. The nanovectors proposed by the NanoAthero consortium to target nanoparticle in order to image “vulnerable” plaques and to deliver therapeutic agents to stabilize the plaques are ready to be transferred to the clinical trial stage.
Indeed, NanoAthero aims to take profit of nanodelivery systems that have been validated and transfer them to proof-of-concept clinical trials. The NanoAthero consortium is a unique opportunity to extend the frontiers of knowledge on atherothrombosis management. Thereby, NanoAthero gathers a store of knowledge ranging from the design of nanosystems, preclinical and clinical validations, through toxicology, to industrial development and production.