# Exploitation of Antimicrobial Nanoparticles and Their Applications in Biomedical Engineering
## 2 Nanomaterials
### Nanomaterials with Antimicrobial Properties
#### 2.3.2 Nanoparticles Combinations with Synergistic Effects  
With regards to the mixture of metallic nanoparticles, one of the major advantages is that they produce a higher antimicrobial effect combined compared to single elemental nanoparticles. [PERSON] et al. investigated the antimicrobial activities of six metal and metal oxide nanoparticles and two of their composites [102]. They found the mean MIC of ZnO and Ag-ZnO composites were, respectively, 437.5 and less than 362.5 \(\upmu\)g/mL, whilst the mean MIC of CuO and Ag-CuO composites were, respectively, 312.5 and less than 237.5 \(\upmu\)g/mL. Both MIC values of the Ag-ZnO and Ag-CuO were significantly lower than the parent materials. There are some advantages to using nanocomposites, such as minimising the utilities of precious and potentially toxic metallic ingredients, which in turn, reduces the cost and may potentially diminish bacterial resistance. Recent AMNP composites claiming to contain Cu, Ag and WC nanoparticles showed stable inhibitions (99.99%) against various deadly pathogens [8].  
In other studies, intermetallic compounds have been studied as antimicrobial agents. Silver-Gold (Ag-Au) alloy nanoparticles combined with penicillin G and piperacillin intensified the antimicrobial effect against _S. aureus_[103]. The authors suggested that such nanoparticles can potentially be used as an adjuvant in combination therapy of antibiotics. It is interesting to note that bimetallic NPs derived from noble Gold and Platinum (Au-Pt) were also found to produce antimicrobial activity against microbes, including multidrug-resistant _E. coli_. Certain bimetallic formulas have been shown to have MIC as low as 5 \(\mu\)g/mL and are still effective against resistant _E. coli_[104].  
A group from China demonstrated the Ti-Ni-Cu shape memory alloys simultaneously possess excellent shape memory effects, cytocompatibility and antibacterial properties after adding a Cu alloying element [105]. The future application of this compound includes biomedical implants and devices with reduced bacterial infections. A recent work showed that the Pt-Ag nanoparticles remarkably enhanced multiple enzyme-mimicking activities related to oxygen reduction reactions and exerted excellent antibacterial effects on _E. coli_ and _S. aureus_[106]. A forthcoming work relates the controllable synthesis of high-quality nanoalloys to their novel catalytic properties for various promising applications, including catalysts, biosensors and biomedicine. Lastly, Table 1 summarizes all mentioned nanoparticles that have been studied for antimicrobial effects.  
\begin{table}
\begin{tabular}{c c c c} \hline
**Monometallic/Metal** & **Mean Size (Shape)** & **Bacteria/Fungi Tested** & **Reference** \\
**Oxide Nanoparticles** & & & _E. coli_ & \\  & 21 nm (cuboctahedron icosahedron & _V. cholerae_ & [73] \\  & and decahedron) & _S. Typhi_ & \\  & & _P. aeruginosa_ & \\  & 12.4 nm & _E. coli_ & [75] \\  & 13.5 nm (spherical) & _E. coli_ & [78] \\ Silver & 39 nm (spherical); & _S. aureus_ & \\ (Ag) & 16 nm (rod) & _E. coli_ & [79] \\  & & _S. epidermidis_ & \\  & & _B. megaterium_ & \\  & 1.5–10 nm (spherical, triangular & _P. aeruginosa_ & \\  & and polyhedron) & _E. coli_ & [80] \\  & & _C. albicans_ & \\  & & _A. niger_ & \\ \hline  & 100 nm (spherical) & _E. coli_ & [88] \\  & 9 nm (quasi-sphere) & _E. coli_ & [89] \\  & & _S. aureus_ & \\  & & _B. subtilis_ & \\  & & _P. aeruginosa_ & \\ Copper & 2–350 nm & _P. aeruginosa_ & [90] \\ (Cu) & & _S. choleraeusus_ & \\  & & _C. albicans_ & \\  & & _K. pneumoniae_ & \\  & & _P. aeruginosa_ & \\  & & _S. parathyroid_ & \\  & & _Shigella_ & \\ \hline  & & EMRSA & \\  & & MRSA & \\  & & _S. aureus_ & \\ Copper oxide & 20–95 nm (rod and rectangle) & _S. epidermidis_ & [47] \\ (CuO) & & _E. coli_ & \\  & & _Protein spp._ & \\  & & _P. aeruginosa_ & \\ \hline \end{tabular}
\end{table}
Table 1: Summary of nanoparticles that have been tested for antimicrobial activity.