Cardiovascular diseases, particularly atherosclerosis has shown great scale of morbidity and mortality worldwide. The circulation of high level of lipoprotein in the blood stream leads to the formation of plaques in intima. On the other hand, the synthetic and pro-inflammatory phenotypic smooth muscle cells (SMCs) further help in the progression of these plaques. The natural process of athero-protection is achieved by reverse cholesterol transport (RCT) and high density lipoprotein (HDL), the smallest member of the lipoprotein family serves a crucial role in the cholesterol removal process from plaque macrophages followed by their transport to the liver for effective excretion. Human atherosclerotic plaques are predominantly M2 macrophages, enriched with macrophage mannose receptor (MMR) on their cell surface in addition to classically activated M1 macrophages. Earlier, we have reported the development of synthetic polymeric hybrid nanoparticle having favorable organ distribution and anti-atherosclerotic property . Herein, we describe the systematic design of a dual targeted synthetic therapeutic NP with both mitochondria and MMR-targeting surface functionalities loaded with a hydrophobic MRI contrast agent, Mito-magneto (MM), to achieve target-specific MRI contrast and therapeutic outcomes in-vivo. Macrophage targeting surface functionality on the HDL-NPs is expected to add another dimension to the construct by targeting plaques and enabling better detection of plaques and enhanced lipid reduction at the same time. In addition, the encapsulation of mitochondria acting coenzyme Q10 (CoQ10) into the core of these NPs is extremely crucial to improve the cellular bioenergetics and reduction of oxidative stress in the SMCs for better prevention and treatment of heart related disease.

Multifunctional therapeutic nanoparticles for atherosclerosis

256th National Meeting (2018)

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