Ru Wen, Shanta Dhar
University of Georgia,
Keywords: HDL, atherosclerosis, RCT
Summary:Atherosclerosis is attributed to coronary heart disease (CHD), a leading cause of death and morbidity worldwide. Reverse cholesterol transport (RCT) is one of the common methods to prevent atherosclerosis. High-density lipoprotein (HDL) provides cardiovascular protection by promoting RCT from peripheral tissues to the liver. As natural nanoparticles (NPs), HDLs have been used as therapeutics, drug delivery vehicles, and imaging agents. Most of the efforts have been made on the reconstituted HDL (rHDL) containing human apolipoprotein AI (ApoAI), nanocrystal HDL, and inorganic-based synthetic HDL. However, these HDLs have potential problems, such as batch-to-batch compatibility and scale-up challenges for rHDL, and safety concerns for inorganic HDL. Our group previously developed a completely synthetic mitochondria-targeted HDL/apoA-I mimicking NP composed of biodegradable polymer, synthetic lipids, and ApoAI mimetic L-4F peptide. Cardiolipin (CL) is a mitochondria-specific phospholipid, maintaining the structural integrity of biological membranes. Therefore, a completely synthetic HDL/apoA-I mimicking NP containing CL as lipid component will participate in the RCT by targeting mitochondria. In this presentation, we will discuss the construction, optimization, and mechanism of action of this newly modified mitochondria targeted CL-based HDL mimicking NPs, and comparison of its activity with previously synthesized HDL-NPs. 1.Marrache S.,Dhar, S., 2013.110(23):9445.