Abstract
Atherosclerosis is one of the world’s most aggressive diseases, claiming over 17.5 million lives per year. This disease is usually caused by high amounts of lipoproteins circulating in the blood stream, which leads to plaque formation. Ultimately, these plaques can undergo thrombosis and lead to major heart damage. A major contributor to these vulnerable plaques is macrophage apoptosis. Development of nanovehicles that carry contrast and therapeutic agents to the mitochondria within these macrophages is attractive for the diagnosis and treatment of atherosclerosis. Here, we report the design and synthesis of a dual-targeted synthetic nanoparticle (NP) to perform the double duty of diagnosis and therapy in atherosclerosis treatment regime. A library of dual-targeted NPs with an encapsulated iron oxide NP, mito-magneto (MM), with a magnetic resonance imaging (MRI) contrast enhancement capability was elucidated. Relaxivity measurements revealed that there is a substantial enhancement in transverse relaxivities upon the encapsulation of MM inside the dual-targeted NPs, highlighting the MRI contrast-enhancing ability of these NPs. Successful in vivo imaging documenting the distribution of MM-encapsulated dual-targeted NPs in the heart and aorta in mice ensured the diagnostic potential. The presence of mannose receptor targeting ligands and the optimization of the NP composition facilitated its ability to perform therapeutic duty by targeting the macrophages at the plaque. These dual-targeted NPs with the encapsulated MM were able to show therapeutic potential and did not trigger any toxic immunogenic response.
