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Table 1 Effects of nanocluster size on antibacterial applications

From: Size and charge effects of metal nanoclusters on antibacterial mechanisms

Material

Target pathogens

Nanocluster size

Result

Antibacterial mechanism

References

Gram-positive bacteria

Gram-negative bacteria

Gold nanoclusters (AuNCs)-6-mercaptohexanoic acid (MHA);

gold nanoparticles (AuNPs)

Staphylococcus aureus and Bacillus subtilis

Escherichia coli and Acinetobacter baumannii

AuNCs = 2.33 ± 0.90 nm;

AuNPs = 7.08 ± 1.5 nm

Compared to larger NPs, AuNCs-MHA have a considerably higher surface area to volume ratio

They may also increase DNA damage, membrane damage, reactive oxygen species (ROS) generation, and metabolic inactivation

[76]

AuNCs-3-mercaptobenzoic acid (MBA)

S. aureus

E. coli

AuNCs =  < 2 nm

Au NPs = 3 and 5 nm

AuNCs-MBA have a high antimicrobial efficacy because of their ultrasmall size

AuNCs of < 2 nm readily passed through ultrasmall pores of the bacteria cell wall, internalizing themselves, and killing the bacteria by simple diffusion

[61]

Luminescent copper nanocluster (CuNC)-doped hydroxyapatite (HAP) NPs

S. aureus MTCC 96 and B. subtilis

MTCC 1305

Green fluorescent protein (GFP) expressing recombinant E. coli, Pseudomonas aeruginosa MTCC 2488, and E. coli DH5α

Doped HAP NPs = 32.64 ± 7 nm and

Undoped HAP NPs = 24.0 ± 6.0 nm;

CuNCs = 1.75 ± 0.3 nm

CuNCs incorporated into doped HAP NPs = 1.71 ± 0.5 nm

Compared to NPs, CuNCs doped with HAP had a lower minimum inhibition concentration (MIC) and exhibited greater antimicrobial activity

Damage to bacterial cell membranes

[100]

AuNCs-MHA

S. aureus, S. epidermidis, B. subtilis

E. coli, P. aeruginosa

AuNCs = ca. 2 nm;

AuNPs = 6.0 ± 3 nm

The improved antibacterial action of AuNCs was determined not just by the ligand identity or its density on the surface but rather by the ultrasmall AuNCs as a whole as an entity and compound. They have a high surface-to-volume ratio because of their extraordinarily diminutive size

Membrane internalization, metabolic imbalance, intracellular ROS production

[79]

Dpep-AgNCs;

Opep-AgNPs

S. aureus

E. coli and Shewanella oneidensis MR-1

Dpep-AgNCs = 1.25 nm;

Opep-AgNPs = ca. 5 nm

Due to the extra-small particles which can increase the potential to permeate into the bacteria, Dpep-AgNCs demonstrated greater antimicrobial activity than Opep-AgNPs

Electrostatic and van der Waals (VDW) forces enable their subsequent internalization

[80]

THPC-AuNPs;

THPC-AuNPs/MTU;

THPC-AuNPs/Prot;

MTU-AuNCs;

Prot/MTU-AuNCs

S. aureus

E. coli

Prot/MTU-AuNCs = ca. 1.5 nm;

AuNPs = not mentioned

Prot/MTU-AuNCs interacted synergistically due to their distinct size and the bacteriostatic properties of the Prot capping shell. THPC-AuNPs caused negligible harm to the bacteria’s membrane cell

Membrane internalization, ROS production

[101]

AuDAMP;

AuAMP;

AuAHMP;

AuDHMP;

S. aureus ATCC29213, methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus faecium (VRE)

E. coli ATCC35218, multidrug-resistant (MDR) A. baumannii, MDR E. coli, MDR P. aeruginosa, MDR K. pneumoniae

AuAMP = 1.8 ± 0.7 nm;

AuDAMP = 1.7 ± 0.5 nm;

AuAHMP = 1.9 ± 0.71 nm;

AuDHMP = 1.7 ± 0.2 nm;

AuNPs-DAMP = ca. 6 nm

Due to their oxidase-like and peroxidase-like nature, AuNCs induced ROS production whereas AuNPs could not, which showed a greater antibacterial effect

Cell membrane destruction, DNA damage, ROS generation

[93]

AgNCs and AgNPs with mercaptosuccinic acid (MSA)

–

P. aeruginosa, A. baumannii, and E. coli

AgNCs = 2.8 nm;

AgNPs = 3.8 and 3.2 nm

In contrast to AgNPs, which tended to self-aggregate outside of bacterial cells, AgNCs had a far higher degree of intracellular localization. Compared to amphiphilic AgNCs, VDW interactions between AgNPs and the hydrophobic tails of DPPE were significantly weaker. In contrast, VDW interactions between AgNPs and the polar heads of lipopolysaccharide (LPS) were significantly more robust. For AgNPs to be able to pass through the membrane, they had to overcome a significantly greater amount of energy

Membrane damage and ROS generation

[99]

  1. DAMP, 4,6-diamino-2-mercaptopyrimidine; AMP, 4-amino-2-mercaptopyrimidine; AHMP, 4-amino-6-hydroxyl-2-mercaptopyrimidine; DHMP, 4,6-dihydroxyl-2-mercaptopyrimidine; DPPE, dipalmitoyl-phosphatidylethamolamine