Target Health Blog

Iridium and Albumin Kill Cancer Cells

February 18, 2019

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The Willamette Meteorite, the sixth-largest meteorite found in the world, has 4.7 ppm iridium and is on display at the American Museum of Natural History in New York City.Photo credit: By User: Dante Alighieri - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1354017

IRIDIUM

Iridium is a chemical 1) ___ and is the second-densest metal (after osmium). It is the most corrosion-resistant metal, even at temperatures as high as 2000?C. Although only certain molten salts and halogens are corrosive to solid iridium, finely divided iridium dust is much more reactive and can be flammable. Iridium is also one of the nine least abundant stable elements in 3) ___ crust; platinum is 10 times more abundant, gold is 40 times more abundant, and silver and mercury are 80 times more abundant. Tellurium is about as abundant as iridium. In contrast to its low abundance in crustal rock, iridium is relatively common in meteorites. The overall concentration of iridium on Earth is thought to be much higher than what is observed in crustal rocks, but because of the density and siderophilic (“iron-loving“) character of iridium, it descended below the crust and into Earth's core when the planet was still molten. As with all of the platinum group 3) ___, iridium can be found naturally in alloys with raw nickel or raw copper. A number of iridium-dominant minerals, with iridium as the species-forming element, are known. They are exceedingly rare and often represent the iridium analogues of the above-given ones. The examples are irarsite and cuproiridsite, to mention some. Within Earth's crust, iridium is found at highest concentrations in three types of geologic structure: igneous deposits (crustal intrusions from below), impact craters, and deposits reworked from one of the former structures. The largest known primary reserves are in the Bushveld igneous complex in South 4) ___, (near the largest known impact crater, the Vredefort crater) though the large copper-nickel deposits near Norilsk in Russia, and the Sudbury Basin (also an impact crater) in Canada are also significant sources of iridium. Smaller reserves are found in the United States. Iridium is also found in secondary deposits, combined with platinum and other platinum group metals in alluvial deposits. The alluvial deposits used by pre-Columbian people in the Choco Department of Colombia are still a source for platinum-group metals. As of 2003, world reserves have not been estimated.

Albumin

The albumins (formed from Latin: albumen “(egg) white; dried egg white“) are a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins are commonly found in blood plasma and differ from other blood proteins in that they are not glycosylated. Substances containing albumins, such as egg 5) ___, are called albuminoids.

A number of blood transport proteins are evolutionarily related, including serum albumin, alpha-fetoprotein, vitamin D-binding protein and afamin. Albumin binds to the cell surface receptor albondin. Serum albumin is the main protein of human blood plasma. Its main function is to regulate blood volume by maintaining the oncotic pressure of 6) ___, also known as colloid osmotic pressure. Alpha-fetoprotein (alpha-fetoglobulin) is a fetal plasma protein that binds various cations, fatty acids and bilirubin. Vitamin D-binding protein binds to vitamin D and its metabolites, as well as to fatty acids. Serum albumin, the most abundant blood plasma protein, is produced in the liver and forms a large proportion of all plasma protein. The human version is human serum albumin, and it normally constitutes about 50% of human plasma protein. Albumin also serve as carriers for molecules of low water solubility, including lipid-soluble hormones, bile salts, unconjugated bilirubin, free fatty acids (apoprotein), calcium, ions (transferrin), and some drugs like warfarin, phenobutazone, clofibrate & phenytoin. For this reason, it is sometimes referred as a molecular “taxi“.

Low albumin (hypoalbuminemia) may be caused by liver disease, nephrotic syndrome, burns, protein-losing enteropathy, malabsorption, malnutrition, late pregnancy, artefact, genetic variations and malignancy. High albumin (hyperalbuminemia) is almost always caused by dehydration. In some cases of retinol, also called, 7 ___deficiency, the albumin level can be elevated to high-normal values. This is because retinol causes cells to swell with water (this is also the reason too much Vitamin A is toxic). This swelling also likely occurs during treatment with 13-cis retinoic acid (isotretnoin), a pharmaceutical for treating severe acne, among other conditions.

New Research

A new compound based on Iridium, hooked onto albumin, can attack the nucleus of cancerous 8) ___ when switched on by light. The treatment of cancer using light, called Photodynamic therapy, is based on chemical compounds called photosensitizers, which can be switched on by 9) ___ to produce oxidizing species, able to kill cancer cells. Clinicians can activate these compounds selectively where the tumor is (using optical fibers) thus killing cancer cells and leaving healthy cells intact. Thanks to the special chemical coating they used, the researchers were able to hook up Iridium to the blood protein Albumin, which then glowed very brightly so they could track its passage into cancer cells, where it converted the cells' own oxygen to a lethal form which killed them. Not only is the newly formed molecule an excellent photosensitizer, but Albumin was able to deliver it into the nucleus inside cancer cells. The dormant compound can then be switched on by light irradiation and destroy the cancer cells from their very center. The bright luminescence of the iridium photosensitizer allowed its accumulation in the nucleus of tumor cells and its activation leading to the cancer cell death to be followed in real time using a microscope. It is amazing that this large protein can penetrate into cancer cells and deliver 10) ___which can kill them selectively on activation with visible light. If this technology can be translated into the clinic, it might be effective against resistant cancers and reduce the side effects of chemotherapy. According to the research team, It is fascinating how albumin can deliver our photosensitizer so specifically to the nucleus.

Sources: University of Warwick: Pingyu Zhang, Huaiyi Huang, Samya Banerjee, Guy J. Clarkson, Chen Ge, Cinzia Imberti, Peter J. Sadler. Nucleus-Targeted Organoiridium-Albumin Conjugate for Photodynamic Cancer Therapy. Angewandte Chemie International Edition, 2019; DOI: 10.1002/anie.201813002; NIH.gov; Wikipedia

ANSWERS: 1) element; 2) Earth's; 3) metals; 4) Africa; 5) white; 6) blood; 7) Vitamin A; 8) cells; 9) light; 10) iridium

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