Dual Targeted Synthetic Nanoparticle for Cardiovascular Diseases.

AAtherosclerosis 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 diagnosis and treatment of atherosclerosis. Here, we report the design and synthesis of a dual targeted synthetic nanoparticle to perform double duty of diagnosis and therapy in atherosclerosis treatment regime. A library of dual targeted nanoparticles (NPs) with an encapsulated iron oxide nanoparticle, mito-magneto with magnetic resonance imaging (MRI) contrast enhancement capabilities were elucidated. Relaxivity measurements revealed that there is substantial enhancement in transverse relaxivities upon encapsulation of mito-magneto inside the dual-targeted NPs highlighting MRI contrast enhancing abilities of these NPs. Successful in vivo imaging documenting distribution of mito-magneto encapsulated dual targeted NPs in the heart and aorta in mice ensured the diagnostic potential. The presence of mannose receptor targeting ligands and optimization of the NP composition facilitated its ability to perform therapeutic duty by targeting the macrophages at the plaque. These dual-targeted NPs with encapsulated mito-magneto were able to show therapeutic potential and did not trigger any toxic immunogenic response.