All Ag Nanoparticles Are Not the Same: Covalent Interactions between Ag Nanoparticles and Nitrile Groups Help Combat Drug‐ and Ag‐Resistant Bacteria

Abstract

Antimicrobial resistance has long been viewed as a lethal threat to global health. Despite the availability of a wide range of antibacterial medicines all around the world, organisms have evolved a resistance mechanism to these therapies. As a result, a scenario has emerged requiring the development of effective antibacterial drugs/agents. In this article, we exclusively highlight a significant finding reported by Zbořil and associates (Adv. Sci. 2021, 2003090). The authors construct a covalently bounded silver‐cyanographene (GCN/Ag) with the antibacterial activity of 30 fold higher than that of free Ag ions or typical Ag nanoparticles (AgNPs). Ascribed to the strong covalent bond between nitrile and Ag, an immense cytocompatibility is shown by the GCN/Ag towards healthy human cells with a minute leaching of Ag ions. Firm interactions between the microbial membrane and the GCN/Ag are confirmed by molecular dynamics simulations, which rule out the dependence of antibacterial activity upon the Ag ions alone. Thus, this study furnishes ample scope to unfold next‐generation hybrid antimicrobial drugs to confront infections arising from drug and Ag‐resistant bacterial strains.

Bacteria-derived extracellular vesicles: endogenous roles, therapeutic potentials and their biomimetics for the treatment and prevention of sepsis

“…The nanoparticles were layered with ICAM-1 antibodies after being loaded with 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide) and ciprofloxacin. The findings of the study revealed that the nanoparticles were able to evade destruction at non-targeted sites and upon interaction with the vascular system of the infected liver tissue, the antibody-coated nanoparticles induced a decrease change in pH and enzymatic alterations, leading to the release of drugs ( 177 , 178 ). These results suggest that the development of a drug-delivery system that mimics EVs could effectively target inflamed liver tissue and hold significant potential for the treatment of sepsis-associated liver injury.…”

Covalent drugs based on small molecules and peptides for disease theranostics

“…Odanacatib 59 and Saxagliptin 60 react with the nucleophilic groups of the target molecule, and the reversible binding makes drugs easier to be metabolized. The nitrile group 61 can improve the drug–target affinity by forming covalent effects. It can reversibly react with the active site Ser or Cys residues to form thiamide adducts by the Pinner reaction because of its electrophilicity.…”

An Overview of Drug Delivery Nanosystems for Sepsis-Related Liver Injury Treatment

“…54 Based on the results of this infectious microenvironment (IME) study, Zhang et al 55 designed a copolymer carrier with a certain pH value and sensitivity to bacterial enzymes (Figure 3) and loaded it with antibiotics (ciprofloxacin) and anti-inflammatory agents (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide), after which the nanoparticles were coated with intercellular adhesion molecule-1 (ICAM-1) antibodies targeting the IME. The results showed that when the antibody-coated nanoparticles came in contact with the vascular system of the infected liver tissue, a reduction in pH and enzymatic changes occurred to achieve drug release, [56][57][58] indicating that targeting inflamed liver tissue was valuable for the treatment of sepsis-associated liver injury.…”