Antimicrobial Gold Nanoclusters Eradicate Escherichia coli Biofilms and Are Nontoxic by Oral Administration

Abstract

Escherichia coli biofilms are a major causative agent of many intestinal infections, and there is ongoing research aimed at E. coli biofilm eradication. Gold nanoclusters (AuNCs) conjugated with various surface ligands have been extensively investigated for antimicrobial properties and provide a potential solution. There is little known about their in vivo safety because current standards of nanosafety research involve incubation of AuNCs with cells in vitro to confirm biocompatibility. In addition to systemic administration, nanosafety research on AuNC-based antimicrobials designed to treat gastrointestinal infections must also consider the potential for inducing gastrointestinal disorders. We report the design and application of two AuNCs coated with either hydroxyl (AuNC@PEG-OH)- or amine (AuNC@PEG-NH2)-functionalized poly­(ethylene glycol), which enables the eradication of E. coli biofilms. Gastrointestinal safety of AuNC@PEG-OH and AuNC@PEG-NH2 was evaluated in healthy mice up to 35 days after administration by oral gavage at a dose of 10 mg/kg (or 1 mg/mL) daily for 14 days. No changes were detected in the histopathology of major organs, serum chemistry, hematology, and feces. Thus, oral administration of AuNCs is unlikely to be of concern for systemic toxicity or in the induction of gastrointestinal illnesses. Further studies on increasing time exposure and doses are necessary to determine whether toxicity occurs at higher doses or whether there is no adverse effect limit.

Peptide-Protected Gold Nanoclusters Efficiently Ameliorate Acute Contact Dermatitis and Psoriasis via Repressing the TNF-α/NF-κB/IL-17A Axis in Keratinocytes

“…The latest studies have demonstrated that, in addition to the excellent physical and chemical properties, pep-AuNCs also exhibit unique intrinsic bioactivities and show good potential in the field of disease diagnosis and treatment [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. AuNCs have been reported to prevent and treat skin infections due to their antimicrobial activity [ 22 , 23 ]. However, their immunomodulatory properties and therapeutic potential in inflammatory skin diseases, such as contact dermatitis and psoriasis, are still unclear.…”

Multiscale Bioresponses of Metal Nanoclusters

“…When administered orally, AuNC@PEG‐OH and AuNC@PEG‐NH 2 demonstrated significant antibiofilm activity without causing notable changes in the blood parameters. [ 209 ]…”

Nanotechnologies for control of pathogenic microbial biofilms

“…12F). 75 Cao et al 91 reported a formulation of functionalized-gold nanoclusters by surface coating with hydroxyl (-OH) or amine (-NH 2 ) functionalized poly(ethylene glycol) in the presence of cell-penetration peptides (YGRKKRRQRRR-(b-ala) 3 -Cys-amide). The formulated nanoclusters (AuNCs@ PEG-OH or AuNCs@PEG-NH 2 ) were found to be effective against gastrointestinal biofilm infection by the causative pathogen, E. coli, demonstrating a remarkable biofilm removal activity at a minimum biofilm eradication concentration (MBEC) of 1 mg mL À1 .…”

“…No toxicity effect was observed when further in vivo studies were conducted. 91 2.2.4 Metal and metal oxide NP formulations for preventing biofilms. One of the strategies for controlling biofilms is to prevent or inhibit their formation by using a variety of nanoparticles.…”