Size and charge effects of metal nanoclusters on antibacterial mechanisms

Abstract

Nanomaterials, specifically metal nanoclusters (NCs), are gaining attention as a promising class of antibacterial agents. Metal NCs exhibit antibacterial properties due to their ultrasmall size, extensive surface area, and well-controlled surface ligands. The antibacterial mechanisms of metal NCs are influenced by two primary factors: size and surface charge. In this review, we summarize the impacts of size and surface charge of metal NCs on the antibacterial mechanisms, their interactions with bacteria, and the factors that influence their antibacterial effects against both gram-negative and gram-positive bacteria. Additionally, we highlight the mechanisms that occur when NCs are negatively or positively charged, and provide examples of their applications as antibacterial agents. A better understanding of relationships between antibacterial activity and the properties of metal NCs will aid in the design and synthesis of nanomaterials for the development of effective antibacterial agents against bacterial infections. Based on the remarkable achievements in the design of metal NCs, this review also presents conclusions on current challenges and future perspectives of metal NCs for both fundamental investigations and practical antibacterial applications.

Keywords: Antibacterial mechanism; Ligand; Metal nanoclusters; Nanomaterials; Size; Surface charge.

Fig. 1

Effects of the size of a metal on it electrical and optical properties

Fig. 2

The pathway and the involved physicochemical challenges while crossing the respective barriers

Fig. 3

Schematic representation of the antimicrobial mechanism of gold nanocarriers (AuNCs) and gold nanoparticles (AuNPs) with p-mercaptobenzoic acid (MBA) as a ligand. Reproduced with permission from ref [61]. Copyright 2021 Elsevier

Fig. 4

Illustration of the difference surface-area-to-volume ratios between bulk material and nanoclusters

Fig. 5

Illustration of catalytic reactions and antibacterial mechanisms of nanoclusters with peroxidase- or oxidase-like enzyme activities. (a) Nanozymes exhibiting peroxidase-like activity facilitate the reduction of H₂O₂, generating highly reactive hydroxyl radicals (·OH). (b) Nanozymes with oxidase-like activity catalyze the conversion of O₂ to singlet oxygen (¹O₂) or even single oxygen atoms. Both ·OH and ¹O₂ serve as potent oxidants, leading to the oxidation of the substrate (S) to ox-substrate (Sox), such as membrane lipids. (c) Nanozymes possessing peroxidase- or oxidase-like activity play a pivotal role in disrupting the membrane structure and degrading the biofilm matrix, thereby exerting antibacterial and antibiofilm effects. This process ultimately results in bacterial cell death. Reproduced with permission from ref [88]. Copyright 2022 MDPI

Fig. 6

Phase one of bacterial adhesion. Reproduced with permission from ref [95]. Copyright 2014 Hindawi

Fig. 7

Interactions of silver nanoparticles (AgNPs) and silver nanoclusters (AgNCs) with bacterial membranes using a coarse-grained molecular dynamics (CGMD) simulation method. Reproduced with permission from ref [99]. Copyright 2020 Nature Publishing Group

Fig. 8

Schematic illustration of the three parts (anchoring point, ligand body, and functional group) of the protecting ligands on gold nanocluster (AuNC) surfaces with mercaptohexanoic acid (MHA) as a ligand model. Reproduced with permission from ref [102]. Copyright 2021 John Wiley and Sons

Fig. 9

An illustration of initial attachment factors of a bacterium to a solid–liquid interface, the interplay between the bacterium’s properties with the solid surface and liquid medium, and physicochemical force probabilities between the bacterium and the solid surface that affect attachment. A Electrostatic interactions; B van der Waals interactions; C hydrophobic interactions. EPS, extracellular polymeric substances; QS, quorum sensing

Fig. 10

Gram-positive and gram-negative bacteria are combated using Dpep-silver nanoclusters (AgNCs) in the antibacterial assay. The Ag + ions that are internalized in both types of bacteria can induce reactive oxygen species (ROS) inside bacterial cells. Dpep-AgNCs internalize into gram-negative bacteria through interactions with lipopolysaccharides (LPS) and porins, while they enter gram-positive bacteria through interactions with peptidoglycan

Fig. 11

Illustration of a bacterium's geometric shape when approaching the surface of a substratum

Fig. 12

Effect of different topographies of the substratum surface on the anti-attachment effects of physicochemical forces of bacteria. Copyright 2019 Frontiers Media S.A. [104] All right reserved

Fig. 13

Schematic illustration of how the surface ligand chemistry of gold nanoclusters (AuNCs) determines their antimicrobial ability. Reproduced with permission from ref [111]. Copyright 2018 American Chemical Society

Fig. 14

Schematic illustration of reactive oxygen species (ROS) generation of cinnamaldehyde (CA)-gold nanoclusters (AuNCs). Reproduced with permission from ref [114]. Copyright 2021 Elsevier

Fig. 15

Schematic illustration of treatment of intracellular bacterial infections with gold nanoclusters conjugated with 4,6-diamino-2-mercaptopyrimidine hydrate (AuDAMP). Reproduced with permission from ref [115]. Copyright 2021 Elsevier