Systematic in vitro toxicological screening of gold nanoparticles designed for nanomedicine applications

Abstract

Gold nanoparticles (AuNP) are increasingly being applied in the biomedical field as therapeutics, contrast agents, and in diagnostic systems, motivating investigations of their toxicity that might arise from accidental exposure. While other work has investigated the toxicological response to gold nanoparticles for industrial purposes, here we have surveyed formulations that have been developed for biomedical use, are in clinical trials or have been FDA-approved. The AuNP library tested contains a range of shapes, inculding spheres, rods and shells, that possess a range of coatings, such as silica, citrate, lipoprotein, polymaleic acid, polyethylene glycol, DNA and others. Good cytocompatibility for all formulations was observed after 1 hour of incubation. However after 24 hours exposure, a nanorod and a spherical DNA coated formulation resulted in toxicity. The coating material was the only factor that influenced toxicity. AuNP exposure seemed to have no effect on cell cytoskeleton deformation and cell spreading. Cell uptake, as measured by computed tomography and ICP-OES, as well as TEM images of cells, confirmed strong AuNP uptake for certain formulations, but there was no correlation with toxicity. No glove translocation occurred, therefore, nitrile gloves are an adequate safety precaution for working with the AuNP studied. In conclusion, the majority of AuNP formulations tested have very low adverse effects.

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo

“…the bone marrow, the liver, and the spleen, confirmed by the TEM of these tissues, which revealed retention in the macrophages. These findings supported the results of Naha et al 12 that typically observed macrophages to be more sensitive to AuNP as compared to epithelial and fibroblast cells, likely due to their higher phagocytic activity and thus higher uptake of nanoparticles. Thus we corroborated the results of Cai et al 9 who demonstrated that AuNP are taken up by the MPS organs.…”

“…Previously, Naha et al . 12 have shown good cytocompatibility in vitro for this AuNP, with no effect on cell cytoskeleton or cell spreading.…”

“…Gold nanoparticles were synthesized, based on previously reported methods 12,53 . The cores were formed by reducing gold chloride via addition of sodium citrate while at boiling point.…”

“…Nanoparticles based on heavy elements, such as gold nanoparticles (AuNP), can overcome the drawbacks of small molecule iodinated CT contrast agents 8–13 . Several groups have demonstrated AuNP to be highly effective x-ray contrast agents, producing stronger contrast than iodinated agents, having the potential to circulate longer than iodinated contrast agents for improved blood pool imaging and possessing high biocompatibility 9,12,14–16 . In addition, gold nanoparticles have been shown to be potent contrast agents for SPCCT 17 and have been shown to be effective imaging agents for characterization of atherosclerosis with a preclinical system 18 .…”

Plasmonic photothermal cancer therapy with gold nanorods/reduced graphene oxide core/shell nanocomposites

“…Graphite flakes, chloroacetic acid, sodium hydroxide, poly(ethyleneglycol)-bis(3-aminopropyl) (NH2PEGNH2, Mw = 1.5 kDa), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (98%, EDC), cetyltrimethylammonium bromide (CTAB), tetrachloroauric acid trihydrate (HAuCl4·3H2O), silver nitrate (AgNO3), ascorbic acid, sodium borohydride (NaBH4), paraformaldehyde, hydrochloric acid, fluorescein-isothiocyanate (FITC), Fluoroshield™ with 1,4-DOI: 10 …”