Nanoparticles – for "bad" cholesterol!

Anton Chugunov, "Biomolecule" 

There is an opinion that the very concept of "cholesterol" does not promise anything good for health, but this substance is an important participant in lipid metabolism, a component of cell membranes and a precursor of sex hormones. Cholesterol becomes "dangerous" only when lipid metabolism is disrupted, and low-density lipoproteins (LDL) begin to predominate in the blood, cholesterol of which can form atherosclerotic plaques. Another soluble protein is the blood lipid complex - high density lipoproteins (HDL) – on the contrary, it removes cholesterol from the blood, transporting it to the liver.

LDL is often called "bad" cholesterol, because cholesterol of this particular fraction forms life-threatening and health-threatening atherosclerotic plaques in the lumen of blood vessels. HDL, on the contrary, was called "good" cholesterol.

Researchers have managed to create artificial HDL based on nanoparticles, which can become a promising means of combating atherosclerosis.

Lipids, which are an indispensable component of life, are insoluble in water (which determines their ability to form biological membranes) and are transported in the bloodstream as part of soluble protein-lipid complexes, among which are high-density lipoproteins (HDL), low-density lipoproteins (LDL), as well as very low-density lipoproteins (VLDL) and chylomicrons, the largest of the lipoproteins, with a diameter from 75 nm to 1.2 microns. Cholesterol (or, as it is more correct to say from the point of view of chemical nomenclature, cholesterol) – the "scourge" of modern civilization and the "culprit" of a large part of cardiovascular diseases (according to public opinion;-) - is part of these complexes in different proportions and with different probability of precipitation (that is, the formation of atherosclerotic plaques in the lumen of blood vessels).

Lipoprotein complexes consist mainly of amphiphilic apolipoprotein proteins and lipids specifically bound by them (mainly cholesterol). The composition of LDL and VLDL includes mainly cholesterol (80% and 90% by weight, respectively), and in HDL content of protein and lipids is approximately equal (≈50%). The particles that make up the HDL nucleus, consisting of apolipoproteins A1 and A2 and phospholipids, are sometimes called disks because of their disc-shaped shape; after cholesterol adsorption, these particles acquire a spherical shape and transfer this lipid to the liver. Cholesterol from the HDL fraction, unlike LDL and VLDL, does not form atherosclerotic plaques, which is why they (fractions) are sometimes called "good" and "bad" cholesterol, respectively.

As a rule, atherosclerosis develops against the background of chronic hypercholesterolemia, but at the origins of the mechanism of this disease lies a violation of lipid metabolism, as a result of which the total cholesterol content increases not so much as the balance between LDL (increases) and HDL (decreases). And if you can lower the "bad" cholesterol by following a diet, then it is quite difficult to increase the HDL content. Scientists from Northwestern University in Chicago have managed to create artificial nanoparticles that are almost identical in parameters to HDL and effectively bind cholesterol [1]. Perhaps in the future it will become a promising means of reducing "bad" cholesterol and a medicine against atherosclerosis.

Gold was chosen as the basis for nanoparticles as a highly inert (i.e., non-toxic) material and suitable for obtaining nanoparticles of the required size. Gold particles are enclosed in a shell of apolipoprotein-1 (apo-A1) and phospholipids, and the result is nanoparticles very similar to HDL in size (≈18 nm in diameter), surface composition and physicochemical properties. The particle, whose golden "core" has a diameter of 5 nm, contains on average 2-5 apo-A1 molecules and ≈80-160 phospholipid molecules.

Synthesis of artificial HDL nanoparticles based on gold (HDL–Au-LF). The "core" of HDL-mimicking nanoparticles are gold particles (≈5 nm), the surface of which is covered with a shell of apolipoprotein A1 (apo-A1) and phospholipids. A phospholipid containing a disulfide group (upper) serves for chemisorption on the surface of a gold particle, and a phospholipid containing an NH ₃⁺ group (lower) – it is contained in native HDL and associates with amphiphilic apo-A1. The "finished" nanoparticles are the same size as natural HDL (≈18 nm). (Figure from [1].)

The resulting nanoparticles effectively adsorb cholesterol from the solution, similar to natural HDL. The interaction constant determined in the experiment on the binding of a fluorescently labeled analog of cholesterol (fluorescence is activated when a substance from the soluble fraction is adsorbed in the nonpolar phase) is ≈3.8 nm, which indicates the great potential of these nanoparticles to combat "bad" cholesterol. (A similar constant for natural HDL is unknown.)

"We have designed a "sponge" for cholesterol. The resulting synthetic nanoparticles have the properties necessary for a drug that reduces cholesterol levels in the blood," says the head of the work Chad Mirkin, professor of chemistry, medicine and materials science and director of the Northwestern International Institute of Nanotechnology. – "Now there are ways and drugs to reduce "bad" cholesterol (LDL), but how to increase HDL levels is unknown. I hope that the nanoparticles we have created will one day find application in this type of treatment" [2].

Literature1. Thaxton C.S., Daniel W.L., Giljohann D.A., Thomas A.D., Mirkin C.A. (2009).
Templated Spherical High Density Lipoprotein Nanoparticles. J. Am. Chem. Soc. doi: 10.1021/ja808856z;
2. ScienceDaily – “Synthetic HDL: New Weapon To Fight Cholesterol Problems”.

Portal "Eternal youth" www.vechnayamolodost.ru16.01.2009