Cardiovascular diseases are major health issues and are one of the leading causes of death and disabilities in the world. An abdominal aortic aneurysm (AAA) is a cardiovascular disease where the abdominal aorta permanently dilatates and weakens. Eventually, the AAA will rupture resulting in massive internal bleeding and death. The disease mainly affects elderly men. A major problem is that no medical treatment is available and patients with large AAA will be offered surgical repair to prevent AAA rupture and deaths. Many pharmacological targets have proven effective in AAA animal models, but so far none have been found effective in humans. Perhaps because the doses needed systemically to reach the damaged aortic wall are so high that it causes many off-target effects, it has a short half-life, or is poorly dissolved in the blood.

This project aims to design drug-filled nanoparticles or microspheres that will be conjugated with a unique antibody, that allows the nanoparticles to accumulate in the damaged aortic wall and release their content in a high concentration locally as it is needed.

To overcome the translational problem of drugs tested in animals fail to work in humans. We plan to establish living slice human AAA cultures that can be used to test the effect of the drug and check the binding abilities of generated nanoparticles designed to reach the AAA wall before more mechanistic testing in rodent AAA models. Furthermore, we have access to multiple artery samples from the Odense Artery Biobank, which will allow us to identify unique target proteins in the AAA wall. In cross-sections of the AAA wall where areas of interest will be micro-dissected by laser capture and analyzed by proteomic analyses. Monoclonal antibodies will be generated and used to direct drug-filled nanoparticles to the damaged aortic wall in vivo. These nanoparticles will be tested in cell culture, and systemically delivered in rodent AAA models and human living AAA slice cultures.  Thereby identifying new therapeutic options for patients living with AAAs.

We need expertise in generating nanoparticles. We provide a platform allowing testing of test compounds that fail to be administered systemically. Our setup can be applied to identify unique targets in human atherosclerotic plaques and other artery-related disease. In the future, we expect that these nanoparticles may be used to deliver epigenetic modulators like miRNAs.