Gold Nanoclusters as Nanoantibiotic Auranofin Analogues.
William NdugireN G Hasitha RavirangaJingzhe LaoOlof RamströmMingdi YanPublished in: Advanced healthcare materials (2021)
Auranofin, a gold(I)-complex with tetraacetylated thioglucose (Ac4 GlcSH) and triethylphosphine ligands, is an FDA-approved drug used as an anti-inflammatory aid in the treatment of rheumatoid arthritis. In repurposing auranofin for other diseases, it was found that the drug showed significant activity against Gram-positive but was inactive against Gram-negative bacteria. Herein, the design and synthesis of gold nanoclusters (AuNCs) based on the structural motif of auranofin are reported. Phosphine-capped AuNCs are synthesized and glycosylated, yielding auranofin analogues with mixed triphenylphosphine monosulfonate (TPPMS)/Ac4 GlcSH ligand shells. These AuNCs are active against both Gram-negative and Gram-positive bacteria, including multidrug-resistant pathogens. Notably, an auranofin analogue, a mixed-ligand 1.6 nm AuNC 4b, is more active than auranofin against Pseudomonas aeruginosa, while exhibiting lower toxicity against human A549 cells. The enhanced antibacterial activity of these AuNCs is characterized by a greater uptake of Au by the bacteria compared to AuI complexes. Additional factors include increased oxidative stress, moderate inhibition of thioredoxin reductase (TrxR), and DNA damage. Most intriguingly, the uptake of AuNCs are not affected by the bacterial outer membrane (OM) barrier or by binding with the extracellular proteins. This contrasts with AuI complexes like auranofin that are susceptible to protein binding and hindered by the OM barrier.
Keyphrases
- gram negative
- multidrug resistant
- oxidative stress
- dna damage
- rheumatoid arthritis
- acinetobacter baumannii
- drug resistant
- pseudomonas aeruginosa
- induced apoptosis
- anti inflammatory
- molecular docking
- high intensity
- label free
- emergency department
- reduced graphene oxide
- cell proliferation
- dna binding
- drug induced
- ischemia reperfusion injury
- disease activity
- electronic health record
- systemic sclerosis
- quantum dots
- interstitial lung disease
- oxide nanoparticles