Gold Nanoparticles Dissolve Extracellularly in the Presence of Human Macrophages

Abstract

Introduction Gold nanoparticles (AuNPs) have the potential to be used in various biomedical applications, partly due to the inertness and stability of gold. Upon intravenous injection, the NPs interact with the mononuclear phagocyte system, first with monocytes in the blood and then with macrophages in tissue. The NP–macrophage interaction will likely affect the stability of the AuNPs, but this is seldom analyzed. This study aimed to elucidate the role of macrophages in the biodissolution of AuNPs and underlying mechanisms. Methods With an in vitro dissolution assay, we used inductively coupled plasma mass spectrometry to quantitatively compare the dissolution of 5 and 20 nm AuNPs coated with citrate or PEG in cell medium alone or in the presence of THP1-derived macrophages at 24 hours. In addition, we analyzed the cell dose, compared extra- and intracellular dissolution, and explored the possible role of reactive nitrogen species. Results The results showed a higher cellular dose of the citrate-coated AuNPs, but dissolution was mainly evident for those sized 5 nm, irrespective of coating. The macrophages clearly assisted the dissolution, which was approximately fivefold higher in the presence of macrophages. The dissolution, however, appeared to take place mainly extracellularly. Acellular experiments demonstrated that peroxynitrite can initiate oxidation of gold, but a ligand is required to keep the gold ions in solution. Conclusion This study suggests extracellular dissolution of AuNPs in the presence of macrophages, likely with the contribution of the release of reactive nitrogen species, and provides new insight into the fate of AuNPs in the body.

Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention

“…This result indicates a higher degradation of internalized particles, leading either to the release of dissolved species or to the generation of nanoparticles. This is in accordance with the existence a macrophage-assisted dissolution of metal particles previously published by others (Kreyling, 1992;McCarrick et al, 2021) .…”

Electrochemical Estimations of the Gold Nanoparticle Size Effect on Cysteine-Gold Oxidation

“…The separation of 5 nm Au NPs from dissolved Au species, which are easily precipitating as Au 0 in dilute solutions and solutions not containing aqua regia, is challenging, but can be achieved in future studies with certain filtering or combined flocculation/centrifugation methods for similar 5 nm Au NPs as in this work. 4,5 It is, however, clear that Au was detected in the electrolyte in this work.…”

“…While Au dissolution in-vivo has been called "unexpected" as late as 2020, 3 it has been shown to occur, especially for oxidative environments containing biomolecules such as ligands or complexing agents and for small Au NPs, i.e. less than 10 nm in size in this study, 4,5 independent of their coating (citrate or polyethylene glycol). 5 Complexation-induced dissolution between Au and different ligands, including chlorides and amino acids, has been reported previously.…”

“…5 Complexation-induced dissolution between Au and different ligands, including chlorides and amino acids, has been reported previously. [6][7][8] Different oxidative environments, including Fenton reactants, 4 triggered macrophages, 4 and a peroxynitrite generator, 5 were only able to increase Au dissolution from 5 nm Au NPs in the presence of other ligands, but not in pure water, sodium chloride, or from 20 or 50 nm Au NPs.…”

Hyaluronic acid-based nanoparticles to deliver drugs to the ocular posterior segment

“…In addition, the topical application of GNPs plays an anti-inflammatory role in endotoxin-induced uveitis (Pereira et al., 2012 ). Thus, with intrinsic antiangiogenic and anti-inflammatory therapeutic properties (Ba Fakih et al., 2020 ; Di Bella et al., 2021 ; McCarrick et al., 2021 ; Kosuge et al., 2022 ), GNPs have the potential to be widely used in the treatment of various neovascular-related retinopathies caused by VEGF and other inflammation-related ocular diseases. In addition to targeting, modification with HA can stabilize GNPs and maintain their penetration capacity in cells and tissues (Li, Ren et al, 2021 ).…”