Theranostic of atherosclerosis using human antibody-targeted multi-modal nanoparticles for in situ delivery of drugs. – ATHERANOS

ATHERANOS project aims at developing a theranostic approach for atherosclerosis which is the main cause of death in the Western world and tends to increase rapidly in developing countries. Atherosclerosis can be regarded as an inflammatory disease that results from an initial activation of the endothelial cells with further enhancement of oxidative stress, lipid and leucocyte recruitment. The lesions evolve to vulnerable plaques presenting large lipid cores covered by a thin fibrous cap at high risk of rupture and thrombi formation, thus precipitating the clinical conditions of stroke and myocardial infarction. Nowadays, there is an increasing interest in molecular imaging in order to assess the cellular components that underlie the risk of rupture. Molecular imaging requires highly sensitive and specific probes made of a signal detection compound and an affinity ligand for targeting. Our project joins in the international competition but what makes it distinct is that it proposes human antibodies (Abs) to functionalize multi-modal nanoparticles loaded with iron oxide and drugs for Magnetic Resonance Imaging (MRI)-guided therapy of atherosclerosis. Human Abs targeting relevant biomarkers of the pathology are mandatory for repeated use in humans in order to avoid immunogenic reactions. The targeted nanoparticles developed until now with murine Abs cannot be directly translated into the clinic. Our project is carried by this will of transfer. MRI is a non-invasive imaging modality which offers the possibility to use safe contrast agents like iron oxide particles. Nucleolipid-based nanoparticles loaded with drug and iron oxide and further functionalized with human antibodies present all the necessary requirements for innocuity. Each partner in ATHERANOS project has the required skills to reach the aim the consortium has set. This multidisciplinary project is supported by the expertise of physicists, chemists, biochemists and molecular biologists. Partner 1 has the know-how for in vivo phage-display selection of human antibodies in animal models of atherosclerosis. This technology is powerful to select antibodies not only for their specificity but also for their targeting capacity in the context of the pathology. Partner 2 has developed and patented a proprietary library comprising several billion of different fully human antibodies and innovative technologies that allow the generation and improvement of high-affinity, human antibody candidates. As an alternative route, in vitro selection will be conducted on pertinent targets. Partner 3 is deeply involved in original approaches for the isolation and production of new molecules for therapeutic application in humans. Partner 4 possesses a large experience in nucleolipid-based nanoparticle construction and efficient drug encapsulation. The expertise developed by each partner in his field offers the necessary guaranties to drive ATHERANOS project to successful pre-clinical development.