Nanomedical approach to prevention and treatment of atherosclerosis

• Applicant: Professorin Iwona Cicha, Ph.D.
• Subject Area: Cardiology, Angiology
• Term: from 2013 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 243858656

Cardiovascular diseases represent one of the biggest global healthproblems, but effective approaches to targeted therapies are stillmissing. The potential clinical impact of nanotechnology in terms ofcardiovascular diseases management is enormous, but no specificnanoparticle-based system has been approved for diagnosis ortherapy of atherosclerosis in humans. In the field of atherosclerosis,magnetic targeting of SPION-loaded cells to vascular stents in orderto prevent thrombosis and restenosis constitutes a promisingpreclinical approach. However, the experimental attempts tomagnetically target drugs to medium and large vessels are veryscarce. Consequently, little is known about the feasibility of magneticdrug targeting approach in atherosclerosis. In the original project, weanalyzed the direct in vitro effect of SPIONs on endothelium,investigated the magnetic targeting of SPIONs using human arteriesex vivo, and established angiography-aided in vivo targeting ofSPIONs in rabbit model. Further, we evaluated the effects of SPIONsconjugated with dexamethasone on atherosclerotic plaques in a rabbitmodel of abdominal aortic atherosclerosis. In this renewal project, wepropose to focus our investigations on magnetic drug targetingapproach to atherosclerosis in order to validate the feasibility ofregion-specific SPION accumulation ex vivo and in vivo. Furthermore,the therapeutic efficacy of the drug-conjugated SPIONs will beextensively investigated in a rabbit model of advancedatherosclerosis. To achieve these objectives, we will at first analysethe effects of blood components on magnetic particle accumulationunder flow ex vivo. The further tasks will be designed to achieve an invivo proof of efficacy studies on magnetic particle accumulation anddrug targeting using drug-loaded SPIONs. For this purpose, we willevaluate the efficacy of SPION delivery to atherosclerotic plaquesusing magnetic resonance imaging and histology. Furthermore, toobtain the preclinical proof of efficacy of the previously developedmarimastat-bound SPIONs and anti-VEGF antibody-conjugatedSPIONs, the magnetic drug targeting studies in atherosclerotic rabbitswill be performed using these nanoparticles. We are convinced thatby increasing the effective local doses of pharmaceutical agents,magnetic drug targeting may represent a useful tool to improve theplaque stability and reduce inflammatory responses.

• DFG Programme: Research Grants