nanoGold and µGold inhibit autoimmune inflammation: a review

Abstract

The newest data on metallic gold have placed the noble metal central in the fight for the safe treatment of autoimmune inflammation. There are two different ways to use gold for the treatment of inflammation: gold microparticles > 20 µm and gold nanoparticles. The injection of gold microparticles (µGold) is a purely local therapy. µGold particles stay put where injected, and gold ions released from them are relatively few and taken up by cells within a sphere of only a few millimeters in diameter from their origin particles. The macrophage-induced release of gold ions may continue for years. Injection of gold nanoparticles (nanoGold), on the other hand, is spread throughout the whole body, and the bio-released gold ions, therefore, affect multitudes of cells all over the body, as when using gold-containing drugs such as Myocrisin. Since macrophages and other phagocytotic cells take up and transport nanoGold and remove it after a short period, repeated treatment is necessary. This review describes the details of the cellular mechanisms that lead to the bio-release of gold ions in µGold and nanoGold.

Keywords: Gold microparticles; Gold nanoparticles; Inflammation; Macrophages; Mast cells.

Fig. 1

Autometallographic (AMG) silver enhancement of gold ion accumulation in the tissue. The tissue sections are exposed to UV light to reduce the gold ions to metallic gold atoms (Au⁰). The resulting nanosized gold particle is enhanced in an AMG developer to study at LM and EM levels. The AMG-enhanced nanoGold-sized particles accumulate in the lysosomes of macrophages, fibroblasts, mast cells, and secretory granules of the mast cells. In this AMG picture, part of a gold grid is shown in the upper part. The dusty appearance of the tissue close to the gold implant represents gold clusters outside cells. The two loaded cells further away are believed to be macrophages (Danscher 2002)

Fig. 2

Autometallographic (AMG) illustration of the dissolucytotic release of the gold ions from a gold grid. a Light micrograph of AMG silver-enhanced J774 cells, grown on a gold grid, packed with silver-enhanced gold nanoparticles (after UV radiation). (1) Heavily loaded cell (arrow). (2) Cell filled with tiny AMG grains (black arrowhead). Such gold-dusted cells were recorded already after 2 days of exposure. (3) Dissolucytes containing coarse AMG grains after 5 days of exposure (white arrowhead). The picture is a mosaic composed of J774 cells grown on gold surfaces for 2 and 5 days, respectively. Scale bar, 20 µm. b Liberation of gold ions into the dissolution membrane. Electron micrograph of a macrophage and its dissolution membrane. The grid to which the cell was attached is removed during the tissue preparation. Notice the AMG-enhanced gold nanoparticles within the membrane. Scale bar, 3 µm. c Electron micrograph of the dissolution membrane to show the AMG grains at higher magnification. Dissolution membrane (dm), cytoplasm (cyt), and nucleus (nuc). Scale bar, 200 nm (Larsen et al. 2007)

Fig. 3

μGold particles (> 20 µm) stay put where they are injected and attract macrophages that liberate gold ions into the intracellular space through dissolucytosis. In contrast, nanoGold particles spread systemically, and in the macrophage lysosomal compartment, there is oxidation to gold ions. The bio-released gold ions (Au⁺), most likely present as dicyanoaurate ions (Au(CN)₂^–) that pharmaceutically influence the intracellular microenvironment as well as macrophages, mast cells, and fibroblasts, that is, the bio-released gold ions affect the immune response, inflammation, and regeneration (Rasmussen et al. 2022)

Fig. 4

Once in the intercellular fluid and the intracellular compartment, the gold ions act in the same ways as systemically administered gold ions. One of the pharmacological effects may be related to the ability of the gold ions to change the folding of the protein structures. (Rasmussen et al. 2022)

Fig. 5

Proteome changes in SF and serum found during treatment indicate involvement of multiple functional pathways and signaling processes, including wound healing, regulation of the humoral and adaptive immune system, and neutrophil degranulation (Rasmussen et al. 2022)