Silver Covalently Bound to Cyanographene Overcomes Bacterial Resistance to Silver Nanoparticles and Antibiotics

• Published in: Advanced science 2021-06, Vol.8 (12), p.2003090-n/a
• Main Authors: Panáček, David, Hochvaldová, Lucie, Bakandritsos, Aristides, Malina, Tomáš, Langer, Michal, Belza, Jan, Martincová, Jana, Večeřová, Renata, Lazar, Petr, Poláková, Kateřina, Kolařík, Jan, Válková, Lucie, Kolář, Milan, Otyepka, Michal, Panáček, Aleš, Zbořil, Radek
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - therapeutic use; Antibiotics; antimicrobial; Antimicrobial agents; Bacteria; Bacterial infections; Bacterial Infections - drug therapy; cytocompatibility; Drug Resistance, Bacterial - drug effects; Fourier transforms; Graphene; Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; Nanomaterials; Nanoparticles; Nitrogen; Silver; Silver - chemistry; Silver - therapeutic use; silver resistant
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202003090

The ability of bacteria to develop resistance to antibiotics is threatening one of the pillars of modern medicine. It was recently understood that bacteria can develop resistance even to silver nanoparticles by starting to produce flagellin, a protein which induces their aggregation and deactivation. This study shows that silver covalently bound to cyanographene (GCN/Ag) kills silver‐nanoparticle‐resistant bacteria at concentrations 30 times lower than silver nanoparticles, a challenge which has been so far unmet. Tested also against multidrug resistant strains, the antibacterial activity of GCN/Ag is systematically found as potent as that of free ionic silver or 10 nm colloidal silver nanoparticles. Owing to the strong and multiple dative bonds between the nitrile groups of cyanographene and silver, as theory and experiments confirm, there is marginal silver ion leaching, even after six months of storage, and thus very high cytocompatibility to human cells. Molecular dynamics simulations suggest strong interaction of GCN/Ag with the bacterial membrane, and as corroborated by experiments, the antibacterial activity does not rely on the release of silver nanoparticles or ions. Endowed with these properties, GCN/Ag shows that rigid supports selectively and densely functionalized with potent silver‐binding ligands, such as cyanographene, may open new avenues against microbial resistance. Silver covalently bound to cyanographene sheets kills persistent bacteria, which are resistant to silver nanoparticles, at trace level concentrations. Owing to the strong and multiple dative bonds between the nitrile groups of cyanographene and silver, there is minimum silver ion leaching, leading eventually to an exceptional combination of antibacterial activity with cytocompatibility.