Gold-based therapy: From past to present

Abstract

Despite an abundant literature on gold nanoparticles use for biomedicine, only a few of the gold-based nanodevices are currently tested in clinical trials, and none of them are approved by health agencies. Conversely, ionic gold has been used for decades to treat human rheumatoid arthritis and benefits from 70-y hindsight on medical use. With a view to open up new perspectives in gold nanoparticles research and medical use, we revisit here the literature on therapeutic gold salts. We first summarize the literature on gold salt pharmacokinetics, therapeutic effects, adverse reactions, and the present repurposing of these ancient drugs. Owing to these readings, we evidence the existence of a common metabolism of gold nanoparticles and gold ions and propose to use gold salts as a "shortcut" to assess the long-term effects of gold nanoparticles, such as their fate and toxicity, which remain challenging questions nowadays. Moreover, one of gold salts side effects (i.e., a blue discoloration of the skin exposed to light) leads us to propose a strategy to biosynthesize large gold nanoparticles from gold salts using light irradiation. These hypotheses, which will be further investigated in the near future, open up new avenues in the field of ionic gold and gold nanoparticles-based therapies.

Keywords: drug repurposing; gold nanoparticles; nanomedicine; nanotoxicity; therapeutic gold salts.

Fig. 1.

Therapeutic gold salts structures and most common names. Structures have been drawn according to PubChem database (https://pubchem.ncbi.nlm.nih.gov/).

Fig. 2.

(A and B) Aurosomes observed in patient’s buttocks skin after chrysotherapy. Magnifications: (A) × 12,000; (B) × 136,000. Reprinted by permission from ref. , Springer Nature: Archives of Dermatological Research, copyright (1990).

Fig. 3.

(A) Case of skin chrysiasis that appears after laser exposure. Reprinted with permission from ref. . (B and C) Aurosomes recrystallization observed in patient’s face skin after chrysotherapy. Large biosynthesized nanoparticle is indicated by a white arrow. Magnifications: (B) × 5,400; (C) × 57,000. Reprinted by permission from ref. , Springer Nature: Archives of Dermatological Research, copyright (1990).

Fig. 4.

(A and B) Transmission electron microscopy observation of human fibroblast incubated with 4-nm GNPs and observed 2 wk after incubation. The dark orange arrows indicate nondegraded GNPs, while light orange arrow shows the structure formed after GNP degradation. Reproduced from ref. .

Fig. 5.

Illustration of cellular metabolism of GNPs and ionic gold, with estimative period for each phenomenon. Illustrations credit: Servier Medical Art (http://smart.servier.com/), which is licensed under CC BY 3.0.

Fig. 6.

(A–D) Aurosomes recrystallization under the electron beam operating at 80 keV during transmission electron microscopy observation. The time lapse between two images is about 2 min. The aurosomes were obtained from 4-nm GNPs 6 mo after incubation in primary human fibroblasts. Original nondegraded nanoparticles can be seen at the right bottom corner. (E) Biotransitions between the different forms of gold, summarizing ancient and recent literature. Illustration credit: Servier Medical Art (http://smart.servier.com/), which is licensed under CC BY 3.0.