Multimetallic NPs, particularly those formed by more than two metals, exhibit rich electronic, optical, and magnetic properties. Multimetallic NP properties, including size and shape, zeta potential, and large surface area, facilitate their efficient interaction with bacterial cell membranes, thereby inducing disruption, reactive oxygen species production, protein dysfunction, DNA damage, and killing potentiated by the host’s immune system.
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Pathogenic bacteria are abundant in the environment. They spread quickly and can easily cause adverse reactions, long-lasting health effects, or even death. Infection originating from the invasion of pathogens into the body is an acute threat to humans, causing diseases, such as pneumonia, gastritis, and sepsis, which can lead to tissue damage, organ failure, and death [1]. Antibiotics have immense benefits in the fight against a diverse range of pathogens. However, mutations are one strategy that bacteria employ to enhance their resistance to antibiotics, leading to the advent of a large number of multidrug-resistant (MDR) strains, which markedly lowers the therapeutic ability of antibiotics. There is increasing concern regarding the generation of antibiotic resistance, as bacteria vigorously persist to emerge with flexible countersteps against conventional antibiotics [2]. This is one of the most notable health-related matters of the 21st century [3]. Infectious diseases caused by MDR bacteria and the abundance of these bacteria have increased at an alarming rate, especially penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, ceftazidime-resistant Klebsiella pneumonia and Escherichia coli, fluoroquinolone-resistant Pseudomonas aeruginosa, and multi-antibiotic resistant Acinetobacter baumannii [4,5]. In addition, various foodborne pathogens associated with Gram-positive bacteria, such as Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Clostridium botulinum, Cronobacter sakazakii, E. coli, Listeria monocytogenes, Salmonella enteritidis, Shigella dysenteriae, S. aureus, Vibrio furnissii, and Yersinia enterocolitica, are causing a large number of diseases, with major effects on public health and safety [6].
Pathogenic bacteria are abundant in the environment. They spread quickly and can easily cause adverse reactions, long-lasting health effects, or even death. Infection originating from the invasion of pathogens into the body is an acute threat to humans, causing diseases, such as pneumonia, gastritis, and sepsis, which can lead to tissue damage, organ failure, and death [1]. Antibiotics have immense benefits in the fight against a diverse range of pathogens. However, mutations are one strategy that bacteria employ to enhance their resistance to antibiotics, leading to the advent of a large number of multidrug-resistant (MDR) strains, which markedly lowers the therapeutic ability of antibiotics. There is increasing concern regarding the generation of antibiotic resistance, as bacteria vigorously persist to emerge with flexible countersteps against conventional antibiotics [2]. This is one of the most notable health-related matters of the 21st century [3]. Infectious diseases caused by MDR bacteria and the abundance of these bacteria have increased at an alarming rate, especially penicillin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, ceftazidime-resistant Klebsiella pneumonia and Escherichia coli, fluoroquinolone-resistant Pseudomonas aeruginosa, and multi-antibiotic resistant Acinetobacter baumannii [4][5]. In addition, various foodborne pathogens associated with Gram-positive bacteria, such as Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Clostridium botulinum, Cronobacter sakazakii, E. coli, Listeria monocytogenes, Salmonella enteritidis, Shigella dysenteriae, S. aureus, Vibrio furnissii, and Yersinia enterocolitica, are causing a large number of diseases, with major effects on public health and safety [6].
The production of new antibiotics requires enormous economic and labor demands and is a time-consuming process. Hence, the development of alternative, unconventional strategies to treat infectious diseases has become highly advisable [7]. The combination of one antimicrobial agent with other antimicrobial agents has many advantages, such as increased biological activity, reduced adverse effects, and increased antimicrobial toxicity of the combined elements. In synergism, one antimicrobial agent influences the activity of the other, and they finally act more efficiently and effectively together due to their different mechanisms of individual action. This may be considered a new approach to solve the problem of bacterial resistance and reduced antimicrobial susceptibility. Thus far, many alternative strategies have been developed to combat MDR bacteria. Among them, several in vitro studies have confirmed the significant antimicrobial activities of combinations of essential oils/plant extracts, conventional antibiotics/plant extracts, and phytochemicals/antibiotics [8].
Nanotechnology has important commercial applications in the fields of biology and medicine, particularly in the areas of drug delivery, diagnosis, tissue engineering, imaging, and bacterial infections [9]. Nanomaterials have special properties owing to their small dimensions; electrical, mechanical, optical, and magnetic properties; thermal stability; and high surface-to-volume ratio [10]. Nanomaterials are considered favorable alternatives to antibiotics for controlling bacterial infections due to a diverse range of factors, such as their size, morphology, surface charge, stability, and concentration in the growth medium. The surface coatings of nanoparticles (NPs) play an important role in influencing the antimicrobial properties of nanomaterials [11,12]. Depending on the number of metals, metal and metal oxide NPs are divided into mono-, bi-, tri-, and quadrometallic types. Among these, bi-, tri-, and multimetallic NPs have attracted the greatest interest due to their enhanced catalytic properties and favorable characteristics compared with monometallic NPs [13]. Multimetallic NPs are novel materials that incorporate two or more metals to make alloys with different functionalities and tunable properties, such as catalytic and optical properties. Multimetallic NPs can be modified by controlling their structure, chemical composition, and morphology to achieve maximum synergistic performance [14]. The addition of one or more metals into the NPs is expected to bring combinatorial effects, such as alteration of the electron structure, deduction of the lattice distance, and improvements in the total electronic charge shift [15]. Therefore, the study of the multidimensional space is warranted.
Nanotechnology has important commercial applications in the fields of biology and medicine, particularly in the areas of drug delivery, diagnosis, tissue engineering, imaging, and bacterial infections [9]. Nanomaterials have special properties owing to their small dimensions; electrical, mechanical, optical, and magnetic properties; thermal stability; and high surface-to-volume ratio [10]. Nanomaterials are considered favorable alternatives to antibiotics for controlling bacterial infections due to a diverse range of factors, such as their size, morphology, surface charge, stability, and concentration in the growth medium. The surface coatings of nanoparticles (NPs) play an important role in influencing the antimicrobial properties of nanomaterials [11][12]. Depending on the number of metals, metal and metal oxide NPs are divided into mono-, bi-, tri-, and quadrometallic types. Among these, bi-, tri-, and multimetallic NPs have attracted the greatest interest due to their enhanced catalytic properties and favorable characteristics compared with monometallic NPs [13]. Multimetallic NPs are novel materials that incorporate two or more metals to make alloys with different functionalities and tunable properties, such as catalytic and optical properties. Multimetallic NPs can be modified by controlling their structure, chemical composition, and morphology to achieve maximum synergistic performance [14]. The addition of one or more metals into the NPs is expected to bring combinatorial effects, such as alteration of the electron structure, deduction of the lattice distance, and improvements in the total electronic charge shift [15]. Therefore, the study of the multidimensional space is warranted.
Monometallic NPs possess only one type of metal with specific chemical and physical properties, such as Ag, Au, Zn, Pd, Cu, Ti, Si, Al, Se, and Mg, which have been used for their antimicrobial activity for centuries. Among these, Ag NPs are the most effective as they are able to kill both Gram-positive and Gram-negative bacteria, and they are even effective against drug-resistant species [16]. Moreover, metal oxide NPs, such as Ag
2
O, ZnO, CuO, TiO
2
, NiO, Fe
3
O
4
, α-Fe
2
O
3
, CaO, MgO, Al
2
O
3
, CeO
2
, Mn
3
O
4
, and ZrO
2
NPs, have highly potent antibacterial effects against a wide spectrum of microorganisms [17]. Similarly, metal sulfide and metal–organic framework (MOF) nanomaterials, such as AgS-, FeS-, CdS-, and ZnS-MOFs and Mn-, Cu-, and Zn-based MOFs, have demonstrated antimicrobial activities [18]. Bimetallic NPs are formed via the integration of two different types of metal atoms to form a single nanometric material with varying structures, morphologies, and properties [19]. Bimetallic NPs can be tuned by selecting the appropriate metal precursors to achieve the desired shape, size, structure, and morphology according to the configuration of atoms, and this finally leads to the formation of alloy, core–shell, and aggregated nanoparticle types [13]. Bimetallic NPs, such as Ag/Au, Ag/Cu, Au/Pt, Au/Pd, Ag/Fe, Fe/Pt, Cu/Zn, Cu/Ni, Au/CuS, and Fe
3
S
4
/Ag NPs, have distinctive surface activities. In addition, bimetallic oxide NPs, such as MgO/ZnO, CuO/ZnO, and Fe
3
O
4/ZnO NPs, due to tensile strain and synergism between the constituent metals, often exhibit unique antibacterial performance.
/ZnO NPs, due to tensile strain and synergism between the constituent metals, often exhibit unique antibacterial performance.
Similarly, trimetallic NPs are made from three different metals for lowering metal consumption, atomic ordering, and fine-tuning the size and morphology of these NPs. Trimetallic NPs exhibit higher catalytic selectivity/activity and efficiency in various applications, such as biomedical, antimicrobial, catalytic, active food packaging, and sensing applications. Moreover, owing to the presence of three metals, there are some possibilities for different structures and morphologies, such as core–shell, mixed structure, subcluster segregated, and multishell [20]. To change their catalytic performance, trimetallic NPs were further designated as alloys and intermetallic NPs by altering the atomic distribution and surface compositions of different metals [21]. Trimetallic NPs exhibit innovative physicochemical properties owing to their synergistic or multifunctional effects for diverse potential applications when compared with monometallic and bimetallic nanomaterials. However, to date, only monometallic, bimetallic, and very few trimetallic NPs have been reported for their antimicrobial effects.
Similarly, trimetallic NPs are made from three different metals for lowering metal consumption, atomic ordering, and fine-tuning the size and morphology of these NPs. Trimetallic NPs exhibit higher catalytic selectivity/activity and efficiency in various applications, such as biomedical, antimicrobial, catalytic, active food packaging, and sensing applications. Moreover, owing to the presence of three metals, there are some possibilities for different structures and morphologies, such as core–shell, mixed structure, subcluster segregated, and multishell [20]. To change their catalytic performance, trimetallic NPs were further designated as alloys and intermetallic NPs by altering the atomic distribution and surface compositions of different metals [21]. Trimetallic NPs exhibit innovative physicochemical properties owing to their synergistic or multifunctional effects for diverse potential applications when compared with monometallic and bimetallic nanomaterials. However, to date, only monometallic, bimetallic, and very few trimetallic NPs have been reported for their antimicrobial effects.
Hence, the distinctive properties of nanomaterials provide a favorable environment for antibacterial therapies when compared with their bulk forms. Many inorganic and organic nanocomposites exhibit potential antibacterial properties with fast and sensitive bacterial detection. Nanocomposites are designed with targeted and sustained release mechanisms, environmental responsiveness, and combinatorial delivery systems for antibacterial therapies [22]. In particular, metal and metal oxide NPs, with nanotoxic mechanisms and collective modes of action, cause membrane damage and produce reactive oxygen species (ROS) that act against bacterial cells [23], which is why pathogens can barely develop resistance against them. The release of metal and metal oxide ions is the main mechanism responsible for the antimicrobial properties of nanocomposites.
Multimetallic NPs, comprising two or more different metals to form alloy or core–shell nanocomposites, have attracted considerable attention as novel materials due to their unique functionalities. The combined action of different metals and metal oxides in a chemical transformation enhances the catalytic performance of multimetallic NPs [24]. Multimetallic NPs with binary, ternary, and quaternary combinations usually have special characteristics, with enhanced chemical, optical, and catalytic properties when compared with mono- and bimetallic NPs, because of the synergistic effects between different metals [14]. Metallic NPs are classified as monometallic, bimetallic, trimetallic, quadrometallic, and so on based on the number of metallic ingredients.
As the name suggests, monometallic NPs compose a single metal species, which compels for the catalytic characteristics of the nanoparticle. Based on the type of metal atom and properties, monometallic NPs are in different forms, like metallic, magnetic, transition metal, and oxide. They can be synthesized by chemical reduction and green synthetic methods, and their structure can be stabilized by various functional groups. Many studies have reported on a wide range of monometallic and metal oxide NPs, and these are used in various catalytic, medical, agricultural, active food packaging, nano-biosensor construction, industrial, and environmental applications. The order of atoms at the nanoscale, which differs from the bulk materials, is due to not only the large surface-area-to-volume ratio but also the specific electronic structure, plasmon excitation, and quantum confinement. In addition, the increased number of kinks, short-range ordering, chemical properties, and ability to store excess electrons also enhance activity. Recent studies on the antimicrobial activity of monometallic and metal oxide NPs are summarized in Table 1, highlighting the size, bacterial strains tested, mode of action, and fabrication techniques used.
Table 1.
Antimicrobial activity of monometallic and metal oxide nanoparticles (NPs).
NPs |
NPs |
---|
Size (nm) |
Size (nm) |
---|
Bacteria |
Bacteria |
---|
Mode of Action |
Mode of Action |
---|
Synthesis |
Synthesis |
---|
Ref. |
Ref. |
---|
Ag |
10 |
V. natriegens |
DNA damage and cell membrane rupture by reactive oxygen species (ROS) |
Green catalysis |
[25] |
Au |
20 |
S. pneumoniae |
Cell lysis |
Chemical reduction |
[26] |
Pd |
13–18 |
S. aureus, S. pyrogens, B. subtilis |
Cell membrane destruction and apoptosis |
Biosynthesis (plant) |
[27] |
Ga |
305 |
M. tuberculosis |
Reduction of the growth of mycobacterium |
Homogenizer |
[28] |
Cu |
15–25 |
S. aureus, B. subtilis |
Synergistic effects of organic functional groups |
Biosynthesis (plant) |
[29] |
Pt |
2–5 |
E. coli, A. hydrophila |
Decrease in the bacterial cell viability and ROS generation |
Chemical reduction |
[30] |
Si |
90–100 |
S. aureus, P. aeruginosa |
Mechanical damage of the bacterial membrane |
Laser ablation |
[31] |
Se |
117 |
Klebsiella sp. |
Production of ROS, disruption of the phospholipid bilayer |
Biosynthesis (plant) |
[32] |
55.9 |
B. subtilis, E. coli |
Ionic interaction between NPs and bacteria-caused cell damage |
Biosynthesis (plant) |
[33] |
|
85 |
E. coli, S. aureus |
Cell membrane damage due to action of ROS |
Laser ablation |
[34] |
|
Ni |
60 |
P. aeruginosa |
Cell membrane destruction |
Biosynthesis (plant) |
[35] |
Mn |
50–100 |
S. aureus, E. coli |
Inactivation of proteins and decrease in the membrane permeability |
Biosynthesis (plant) |
[36] |
Fe |
474 |
E. coli. |
Attraction between negatively charged cell membrane and NPs |
Biosynthesis (plant) |
[37] |
Bi |
40 |
B. anthracis, C. jejuni, E. coli, M. arginini |
Inhibition of protein synthesis |
Chemical condensation |
[38] |
Ag2O |
10–60 |
S. mutans, L. acidophilus |
Penetration of the cells and hindrance of the growth of the pathogen |
Biosynthesis (plant) |
[39] |
CuO |
60 |
B. cereus |
Disturbance of various biochemical processes when copper ions invade inside the cells |
Biosynthesis (plant) |
[40] |
ZnO |
30 |
A. baumannii |
Increase in the production of ROS |
Sol–gel and biosynthesis |
[41] |
TiO2 |
9.2 |
E. coli |
Decomposition of outer cell membrane by ROS, primarily hydroxyl radicals (OH.) |
Biosynthesis (plant) |
[42] |
NiO |
40–100 |
B. subtilis, E. coli |
Induction of membrane damage by oxidative stress created at the NiO NP interface |
Hydrothermal |
[43] |
Fe3O4 |
25–40 |
S. aureus, E. coli, S. dysentery |
Cellular enzyme deactivation and disruption in plasma membrane permeability |
Coprecipitation |
[44] |
α-Fe2O3 |
16 |
B. subtilis, S. aureus, E. coli, K. pneumonia |
Desorption of membrane by the generated free radicals, including O2. and OH. |
Biosynthesis (plant) |
[45] |
CaO |
58 |
E. coli, S. aureus, K. pneumonia |
Cell membrane destruction |
Biosynthesis (plant) |
[46] |
MgO |
27 |
Bacillus sp., E. coli |
Destruction of cell membrane integrity resulting in leakage of intracellular materials |
Ultrasonication |
[47] |
Al2O3 |
30–50 |
F. oxysporum, S. typhi, A. flavus, C. violaceum |
Decomposition of bacterial outer membranes by ROS |
Biosynthesis (fungi) |
[48] |
CeO2 |
5–20 |
L. monocytogenes, E. coli, B. cereus |
ROS generation by CeO2 as a pro-oxidant |
Precipitation |
[49] |
Mn3O4 |
130 |
K. pneumonia, P. aeruginosa |
Membrane damage of bacterial cells by the easy penetration of Mn3O4 NPs |
Hydrothermal |
[50] |
ZrO2 |
2.5 |
S. mutans, S. mitis, R. dentocariosa, R. mucilaginosa |
Enhancement of the interactions between NPs and bacterial constituents |
Solvothermal |
[51] |
Ag2S |
65 |
Phormidium spp. |
Inhibition of cell membrane by Ag2S NPs, resulting in harmful effects on other biological activities |
Chemical reduction |
[52] |
ZnS |
65 |
Streptococcus sp., S. aureus, Lactobacillus sp., C. albicans |
Dischargement of ions, which react with the thiol groups in the proteins present on the cell membrane |
Biosynthesis (bacteria) |
[53] |
CdS |
25 |
Streptococcus sp., S. aureus, Lactobacillus sp., C. albicans |
Impregnation and surrounding the bacterial cells by CdS NPs |
Biosynthesis (bacteria) |
[53] |
FeS |
35 |
S. aureus, E. coli, E. faecalis |
NP internalization through the fine cell membrane |
Hydrothermal |
[54] |
Mn-MOF |
˗ |
E. coli, E. faecalis, S. aureus, P. aeruginosa |
Peptide–nalidixic acid conjugate formation |
Mechanochemical |
[55] |
Mg-MOF |
˗ |
E. coli, E. faecalis, S. aureus, P. aeruginosa |
Peptide–nalidixic acid conjugate formation |
Mechanochemical |
[55] |
Ag-MOF |
˗ |
S. aureus |
High stability in water and the existence of Ag ion |
Solvothermal |
[56] |
Cu-MOF |
˗ |
S. aureus E. coli, K. pneumonia, P. aeruginosa, S. aureus |
Attachment to the bacterial surfaces by active surface metal sites in Cu-MOF |
Hydrothermal |
[57] |
Zn-MOF |
˗ |
P. aeruginosa |
Penetration inside the bacteria, causing cell damage by interaction with lipotropic acid |
Solvothermal |
[58] |
Co-MOF |
˗ |
E. coli |
Strong interaction with membranes containing glycerophosphoryl moieties |
Hydro-solvothermal |
[59] |
Ag | 10 | V. natriegens | DNA damage and cell membrane rupture by reactive oxygen species (ROS) | Green catalysis | [25] |
Au | 20 | S. pneumoniae | Cell lysis | Chemical reduction | [26] |
Pd | 13–18 | S. aureus, S. pyrogens, B. subtilis | Cell membrane destruction and apoptosis | Biosynthesis (plant) | [27] |
Ga | 305 | M. tuberculosis | Reduction of the growth of mycobacterium | Homogenizer | [28] |
Cu | 15–25 | S. aureus, B. subtilis | Synergistic effects of organic functional groups | Biosynthesis (plant) | [29] |
Pt | 2–5 | E. coli, A. hydrophila | Decrease in the bacterial cell viability and ROS generation | Chemical reduction | [30] |
Si | 90–100 | S. aureus, P. aeruginosa | Mechanical damage of the bacterial membrane | Laser ablation | [31] |
Se | 117 | Klebsiella sp. | Production of ROS, disruption of the phospholipid bilayer | Biosynthesis (plant) | [32] |
55.9 | B. subtilis, E. coli | Ionic interaction between NPs and bacteria-caused cell damage | Biosynthesis (plant) | [33] | |
85 | E. coli, S. aureus | Cell membrane damage due to action of ROS | Laser ablation | [34] | |
Ni | 60 | P. aeruginosa | Cell membrane destruction | Biosynthesis (plant) | [35] |
Mn | 50–100 | S. aureus, E. coli | Inactivation of proteins and decrease in the membrane permeability | Biosynthesis (plant) | [36] |
Fe | 474 | E. coli. | Attraction between negatively charged cell membrane and NPs | Biosynthesis (plant) | [37] |
Bi | 40 | B. anthracis, C. jejuni, E. coli, M. arginini | Inhibition of protein synthesis | Chemical condensation | [38] |
Ag2O | 10–60 | S. mutans, L. acidophilus | Penetration of the cells and hindrance of the growth of the pathogen | Biosynthesis (plant) | [39] |
CuO | 60 | B. cereus | Disturbance of various biochemical processes when copper ions invade inside the cells | Biosynthesis (plant) | [40] |
ZnO | 30 | A. baumannii | Increase in the production of ROS | Sol–gel and biosynthesis | [41] |
TiO2 | 9.2 | E. coli | Decomposition of outer cell membrane by ROS, primarily hydroxyl radicals (OH·) | Biosynthesis (plant) | [42] |
NiO | 40–100 | B. subtilis, E. coli | Induction of membrane damage by oxidative stress created at the NiO NP interface | Hydrothermal | [43] |
Fe3O4 | 25–40 | S. aureus, E. coli, S. dysentery | Cellular enzyme deactivation and disruption in plasma membrane permeability | Coprecipitation | [44] |
α-Fe2O3 | 16 | B. subtilis, S. aureus, E. coli, K. pneumonia | Desorption of membrane by the generated free radicals, including O2· and OH· | Biosynthesis (plant) | [45] |
CaO | 58 | E. coli, S. aureus, K. pneumonia | Cell membrane destruction | Biosynthesis (plant) | [46] |
MgO | 27 | Bacillus sp., E. coli | Destruction of cell membrane integrity resulting in leakage of intracellular materials | Ultrasonication | [47] |
Al2O3 | 30–50 | F. oxysporum, S. typhi, A. flavus, C. violaceum | Decomposition of bacterial outer membranes by ROS | Biosynthesis (fungi) | [48] |
CeO2 | 5–20 | L. monocytogenes, E. coli, B. cereus | ROS generation by CeO2 as a pro-oxidant | Precipitation | [49] |
Mn3O4 | 130 | K. pneumonia, P. aeruginosa | Membrane damage of bacterial cells by the easy penetration of Mn3O4 NPs | Hydrothermal | [50] |
ZrO2 | 2.5 | S. mutans, S. mitis, R. dentocariosa, R. mucilaginosa | Enhancement of the interactions between NPs and bacterial constituents | Solvothermal | [51] |
Ag2S | 65 | Phormidium spp. | Inhibition of cell membrane by Ag2S NPs, resulting in harmful effects on other biological activities | Chemical reduction | [52] |
ZnS | 65 | Streptococcus sp., S. aureus, Lactobacillus sp., C. albicans | Dischargement of ions, which react with the thiol groups in the proteins present on the cell membrane | Biosynthesis (bacteria) | [53] |
CdS | 25 | Streptococcus sp., S. aureus, Lactobacillus sp., C. albicans | Impregnation and surrounding the bacterial cells by CdS NPs | Biosynthesis (bacteria) | [53] |
FeS | 35 | S. aureus, E. coli, E. faecalis | NP internalization through the fine cell membrane | Hydrothermal | [54] |
Mn-MOF | ˗ | E. coli, E. faecalis, S. aureus, P. aeruginosa | Peptide–nalidixic acid conjugate formation | Mechanochemical | [55] |
Mg-MOF | ˗ | E. coli, E. faecalis, S. aureus, P. aeruginosa | Peptide–nalidixic acid conjugate formation | Mechanochemical | [55] |
Ag-MOF | ˗ | S. aureus | High stability in water and the existence of Ag ion | Solvothermal | [56] |
Cu-MOF | ˗ | S. aureus, E. coli, K. pneumonia, P. aeruginosa, S. aureus | Attachment to the bacterial surfaces by active surface metal sites in Cu-MOF | Hydrothermal | [57] |
Zn-MOF | ˗ | P. aeruginosa | Penetration inside the bacteria, causing cell damage by interaction with lipotropic acid | Solvothermal | [58] |
Co-MOF | ˗ | E. coli | Strong interaction with membranes containing glycerophosphoryl moieties | Hydro-solvothermal | [59] |
Bimetallic NPs have attracted huge attention due to their modified properties, and they can be prepared in different sizes, shapes, and structure with a combination of different metals.
Extensive studies in the past decade investigated the use of bimetallic NPs as a new advancement in the field of research and as technological domains to increase efficiency. Owing to the distinct catalytic and synergistic properties between two different metals, bimetallic NPs have potential applications in more fields than their corresponding monometallic one. Depending on their physical and chemical interactions, the spatial overlapping and distribution of two atoms can lead to the formation of a core–shell or simply an alloy due to the impact of individual metals [60]. The addition of a second metal is a major technique for tuning the geometric and electronic structures of NPs to increase their catalytic activity and selectivity. The size, shape, and morphology of alloy or core–shell NPs are comparatively different from those of the individual metals, thereby creating novel opportunities for a range of biomedical applications [61]. The antimicrobial activity of bimetallic NPs has been assessed against numerous types of pathogenic bacteria, especially E. coli, P. aeruginosa, and S. mutans, which are mainly responsible for human epidemics. Bimetallic NPs exhibit remarkable performance compared with commonly used antibiotics and other antimicrobial treatments, as pathogens cannot develop resistance to them because they suppress the generation of biofilms and accelerate other correlated processes [62].
Trimetallic NPs have favorable properties, such as physical, chemical, and tunable properties, when compared with mono- and bimetallic NPs, which result in multiple applications for these NPs. These favorable properties are due to multifunctional or synergistic effects produced by the three metals present in the same system [20]. The addition of a third metal or metal oxide into the composite supposedly generates a combinatorial effect and introduces several possibilities for different morphologies, structures, and chemical compositions to improve catalytic activity, selectivity, and specific performance [63]. Trimetallic NPs exhibit improved reactivity because of the electronic and synergistic effects of the different elements and the geometric arrangements of the metal surrounding the absorbing atoms. At this coherence, the properties of the materials are altered due to electron transfer effects, lattice mismatching, and surface rearrangement [64]. Consequently, trimetallic NPs, such as Fe/Co/Ni supported on multiwalled carbon nanotubes (MWCNTs), show efficient and enhanced bifunctional performance for the oxygen reduction and oxygen evolution reactions [65]. Similarly, Cu/Au/Pt, with high catalytic activity and excellent killing performance for biosensing and cancer theranostics [66], and Pd/Cu/Au, as excellent temperature sensors and fluorescence detectors of H2O2 and glucose [67], have attracted attention as promising catalysts. Hence, trimetallic NPs exhibit potent antibacterial activity and have been found to be more effective agents than bimetallic and monometallic NPs, even at lower metal concentrations.
Higher-order quadrometallic NPs are made from four different metals for various applications with different fabrication methods. Recently, solid-state dewetting of Ag/Pt/Au/Pd quadrometallic NPs on sapphire has been prepared successfully with tunable localized surface plasmon resonance [68]. Similarly, Ag/Cu/Pt/Pd quadrometallic NPs prepared by seed-mediated growth, where small Pt and Pd NPs were attached on the surface of AgCu Janus bimetallic NPs as seeds in an aqueous solution [69], and heterostructured Pt/Pd/Rh/Au tetrahexahedral multimetallic NPs were synthesized through alloying/dealloying with Bi in a tube furnace [70]. Moreover, to date, there has been no investigation into the antimicrobial properties of quadrometallic and multimetallic NPs. Table 2 summarizes bi- and trimetallic NPs used for antibacterial activity with an array of sizes, strains tested, mechanisms, and synthetic methods.
Table 2. Antimicrobial activity of bimetallic and trimetallic NPs.
NPs |
NPs |
---|
Size (nm) |
Size (nm) |
---|
Bacteria |
Bacteria |
---|
Mode of Action |
Mode of Action |
---|
Synthesis |
Synthesis |
---|
Ref. |
Ref. |
---|
Ag/Au |
9.7 |
E. coli, S. aureus |
Increased production of ROS |
Green |
[71] |
|
Ag/Cu |
26 |
E. coli, B. subtilis |
Permeability of copper and silver ions into the bacterial cell membrane |
Biosynthesis (plant) |
[72] |
|
Au/Pt |
2–10 |
S. aureus, P. aeruginosa, C. albicans |
Release of Ag+ ions, unbalance of cell metabolism, and ROS generation |
Chemical reduction |
[73] |
|
Ag/Fe |
110 |
S. aureus, P. aeruginosa |
Release of Ag+ ions and ROS generation |
Electrical explosion |
[74] |
|
Ag/Pt |
36 |
E. faecalis, E. coli |
Increased production of ROS |
Biosynthesis (plant) |
[75] |
|
Cu/Zn |
100 |
A. faecalis, S. aureus, C. freundii |
Synergistic properties of Zn2+ and Cu2+ ions together |
Biosynthesis (plant) |
[76] |
|
Cu–Ni |
25 |
S. mutans, S. aureus, E. coli |
Strong adsorption of ions to the bacterial cells |
Chemical reduction |
[77] |
|
Ag/ZnO |
43 |
S. aureus, P. aeruginosa |
Ag+ leaching from metallic silver |
Photoreduction |
[78] |
|
Ag/SnO2 |
9 |
B. subtilis, P. aeruginosa, E. coli |
Synergistic properties of Ag and SnO |
Biosynthesis (plant) |
[79] |
|
Cu/FeO2 |
32.4 |
B. subtilis, X. campestris |
DNA damage induced by NPs |
Hydrothermal |
[80] |
|
Au/CuS |
2–5 |
B. anthracis |
Disordered and damaged membranes |
Seeded |
[81] |
|
Fe3S4/Ag |
226 |
S. aureus, E. coli |
Release of Ag+ ions and ROS generation |
Solvothermal |
[82] |
|
MgO/ZnO |
10 |
P. mirabilis |
Alteration of cell membrane activity, ion release, and ROS production |
Precipitation |
[83] |
|
CuO/ZnO, |
50 and 82 |
E. coli, S. aureus |
Electrostatic interaction causing to change membrane permeability on account of depolarization |
Electrical explosion |
[84] |
|
CuO/Ag |
20–100 |
L. innocua, S. enteritidis |
Binding of the ions released by μCuO/nAg to the thiol groups of many enzymes in cell membrane |
Hydrothermal |
[85] |
|
Fe3O4/ZnO, |
200–800 |
S. aureus, E. coli |
Membrane stress, disrupting and damaging cell membrane |
Coprecipitation |
[86] |
|
CeO2/FeO2 |
40 and 25 |
P. aeruginosa |
Combination of NPs with antibiotic ciprofloxacin, causing inhibitory effect on bacterial growth and biofilm formation |
Hydrothermal |
[87] |
|
Cu/Zn/Fe |
42 |
E. faecalis, E. coli |
Interruption of cellular processes by released ions, which can cross cell membranes |
Chemical reduction |
[88] |
|
Au/Pt/Ag |
20–40 |
E. coli, S. typhi, E. faecalis |
Generation of ROS |
Microwave |
[89] |
|
Cu/Cr/Ni |
100–200 |
E. coli, S. aureus |
Antibacterial activity of trimetallic NPs in comparison with pure metals |
Biosynthesis (plant) |
[63] |
|
CuO/NiO/ZnO |
7 |
S. aureus, E. coli |
Ruptured and cracked bacterial cells by the release of intracellular components |
Coprecipitation |
[90] |
|
Ag/ZnO/TiO2 |
60–170 |
E. coli |
Reduction in the bandgap energy by increasing the e− & h+ charge separation time |
Sol–gel |
[91] |
Ag/Au | 9.7 | E. coli, S. aureus | Increased production of ROS | Green | [71] |
Ag/Cu | 26 | E. coli, B. subtilis | Permeability of copper and silver ions into the bacterial cell membrane | Biosynthesis (plant) | [72] |
Au/Pt | 2–10 | S. aureus, P. aeruginosa, C. albicans | Release of Ag+ ions, unbalance of cell metabolism, and ROS generation | Chemical reduction | [73] |
Ag/Fe | 110 | S. aureus, P. aeruginosa | Release of Ag+ ions and ROS generation | Electrical explosion | [74] |
Ag/Pt | 36 | E. faecalis, E. coli | Increased production of ROS | Biosynthesis (plant) | [75] |
Cu/Zn | 100 | A. faecalis, S. aureus, C. freundii | Synergistic properties of Zn2+ and Cu2+ ions together | Biosynthesis (plant) | [76] |
Cu–Ni | 25 | S. mutans, S. aureus, E. coli | Strong adsorption of ions to the bacterial cells | Chemical reduction | [77] |
Ag/ZnO | 43 | S. aureus, P. aeruginosa | Ag+ leaching from metallic silver | Photoreduction | [78] |
Ag/SnO2 | 9 | B. subtilis, P. aeruginosa, E. coli | Synergistic properties of Ag and SnO | Biosynthesis (plant) | [79] |
Cu/FeO2 | 32.4 | B. subtilis, X. campestris | DNA damage induced by NPs | Hydrothermal | [80] |
Au/CuS | 2–5 | B. anthracis | Disordered and damaged membranes | Seeded | [81] |
Fe3S4/Ag | 226 | S. aureus, E. coli | Release of Ag+ions and ROS generation | Solvothermal | [82] |
MgO/ZnO | 10 | P. mirabilis | Alteration of cell membrane activity, ion release, and ROS production | Precipitation | [83] |
CuO/ZnO, | 50 and 82 | E. coli, S. aureus | Electrostatic interaction causing to change membrane permeability on account of depolarization | Electrical explosion | [84] |
CuO/Ag | 20–100 | L. innocua, S. enteritidis | Binding of the ions released by μCuO/nAg to the thiol groups of many enzymes in cell membrane | Hydrothermal | [85] |
Fe3O4/ZnO, | 200–800 | S. aureus, E. coli | Membrane stress, disrupting and damaging cell membrane | Coprecipitation | [86] |
CeO2/FeO2 | 40 and 25 | P. aeruginosa | Combination of NPs with antibiotic ciprofloxacin, causing inhibitory effect on bacterial growth and biofilm formation | Hydrothermal | [87] |
Cu/Zn/Fe | 42 | E. faecalis, E. coli | Interruption of cellular processes by released ions, which can cross cell membranes | Chemical reduction | [88] |
Au/Pt/Ag | 20–40 | E. coli, S. typhi, E. faecalis | Generation of ROS | Microwave | [89] |
Cu/Cr/Ni | 100–200 | E. coli, S. aureus | Antibacterial activity of trimetallic NPs in comparison with pure metals | Biosynthesis (plant) | [63] |
CuO/NiO/ZnO | 7 | S. aureus, E. coli | Ruptured and cracked bacterial cells by the release of intracellular components | Coprecipitation | [90] |
Ag/ZnO/TiO2 | 60–170 | E. coli | Reduction in the bandgap energy by increasing the e− & h+ charge separation time | Sol–gel | [91] |