Artificial High Density Lipoprotein Nanoparticles in Cardiovascular Research

Abstract

Lipoproteins are endogenous nanoparticles which are the major transporter of fats and cholesterol in the human body. They play a key role in the regulatory mechanisms of cardiovascular events. Lipoproteins can be modified and manipulated to act as drug delivery systems or nanocarriers for contrast agents. In particular, high density lipoproteins (HDL), which are the smallest class of lipoproteins, can be synthetically engineered either as nascent HDL nanodiscs or spherical HDL nanoparticles. Reconstituted HDL (rHDL) particles are formed by self-assembly of various lipids and apolipoprotein AI (apo-AI). A variety of substances including drugs, nucleic acids, signal emitting molecules, or dyes can be loaded, making them efficient nanocarriers for therapeutic applications or medical diagnostics. This review provides an overview about synthesis techniques, physicochemical properties of rHDL nanoparticles, and structural determinants for rHDL function. We discuss recent developments utilizing either apo-AI or apo-AI mimetic peptides for the design of pharmaceutical rHDL formulations. Advantages, limitations, challenges, and prospects for clinical translation are evaluated with a special focus on promising strategies for the treatment and diagnosis of atherosclerosis and cardiovascular diseases.

High Density Lipoproteins: Metabolism, Function, and Therapeutic Potential

“…While conjugations of HDLs have mostly been used to target the liver, where SR-B1 expression is high, it has been found that the addition of folic acid to HDLs expands the target organ pool to cells expressing the folate receptor (119). The current understanding of how to encapsulate vaso-protective compounds within rHDL allows us to consider using it a treatment (120). The infusion of rHDL loaded with a potent LXR agonist enabled atherosclerotic plaque regression in the apoE-knock out mouse model, with significant accumulation of the synthetic HDL found in the atherosclerotic lesions (121).…”

Interface of Phospholipase Activity, Immune Cell Function, and Atherosclerosis

“…Future work would need to find ways to target phospholipases within the plaque. Numerous small-molecule inhibitors of phospholipase are known, and pairing with nanotechnology may be feasible [ 155 ]. The dual function of lipin-1 may also represent an interesting target for atherosclerosis therapeutics.…”

Immunomodulatory Nanomedicine for the Treatment of Atherosclerosis

“…As the LDL-receptor is not only expressed on hepatocytes, but also on other cells like antigen-presenting cells, LNPs can target a variety of cell-types to exert its effects and modulate lipid and/or inflammatory mechanisms ( Figure 1 ). Another lipoprotein that has been encapsulated into LNPs for receptor-mediated uptake is ApoA1, which has been extensively discussed in another review [ 37 ] and which will therefore only be briefly highlighted here. ApoA1 is the main protein that is present in high density lipoprotein (HDL) and is taken up in the liver via the scavenger receptor class B type I (SR-B1).…”