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Magnetic Functionalized Nanoparticles for Biomedical, Drug Delivery and Imaging Applications


Medicine is constantly looking for new and improved treatments for diseases, which need to have a high efficacy and be cost-effective, creating a large demand on scientific research to discover such new treatments. One important aspect of any treatment is the ability to be able to target only the illness and not cause harm to another healthy part of the body. For this reason, metallic nanoparticles have been and are currently being extensively researched for their possible medical uses, including medical imaging, antibacterial and antiviral applications. Superparamagnetic metal nanoparticles possess properties that allow them to be directed around the body with a magnetic field or directed to a magnetic implant, which opens up the potential to conjugate various bio-cargos to the nanoparticles that could then be directed for treatment in the body. Here we report on some of the current bio-medical applications of various metal nanoparticles, including single metal nanoparticles, functionalized metal nanoparticles, and core-shell metal nanoparticles using a core of Fe3O4 as well as synthesis methods of these core-shell nanoparticles.


Metal nanomaterials represent a significant doorway for the future of medicine. Although there is still much unknown about the long-term safety of metal nanoparticles in medicine [1], these particles have already found their place within various biomedical applications such as site-specific imaging in vivo [2,3,4], cancer detection [5, 6], cancer therapy [7,8,9,10], neurodegenerative disease therapy [11,12,13], HIV/AIDS therapy [14,15,16], ocular disease therapy [17,18,19], and respiratory disease therapy [20, 21]. Figure 1 presents a range of current uses for nanoparticles in medicine. Despite the recent advances in nanomedicine, there are still many obstacles in the way of nano-therapy, such as it can be hard to achieve a synthesis route which produces easily repeatable results, with many nanoparticle synthesis methods producing a range in both size [22,23,24] and shape [25,26,27,28] of nanoparticles and/or do not produce the nanomaterials in a large enough quantity to make it economically viable [29]. Another key factor is that it is relatively unknown as to the long-term toxicity of some nanoparticles over a period of time due to how relatively new the field of research is [30,31,32]. Among the many possible uses of metal nanoparticles lies the area of drug delivery [33, 34]. Due to the large surface area that nanoparticles provide [35], they possess the ability to be able to deliver large quantities of drugs or other medical cargoes [36]. An alternative to single metal nanoparticles is to incorporate a core to the nanoparticle which has alternative properties to the shell material, and one example of this is to incorporate a magnetic core. One challenge that still presents itself is synthesizing core-shell nanoparticles; there are many ways to synthesize nanoparticles [37], but new challenges emerge when attempting to synthesize a core-shell nanoparticle [38].

Fig. 1
figure 1

Some of the current uses of nanoparticles in medicine

This review first focuses on some of the methods currently used to generate core-shell nanoparticles focusing on using cores of Fe3O4 and coatings of gold or silver. We then examine current bio-medical applications of single metal nanoparticles, their limitations, and how to overcome them with the application of magnetic cores.

Synthesis of Core-Shell Nanoparticles

Methods for the synthesis of metallic nanoparticles have been known for many years, for example, Stevenson et al. published a synthesis for gold nanoparticles via the reduction of HAuCl4 in 1951 [39]. Since then, there have been many different routes for nanoparticle synthesis such as gas deposition [40], sol-gel [41], and aerosol/vapor phase [42]. However, a new challenge presents itself when attempting to synthesize metal nanoparticles consisting of a core-shell structure, in which one metal forms the core and a second metal forms the shell, for example Fe particles degrade in water, whilst HAuCl4 is a strong oxidizing agent [38]. One such example that will be discussed further is using a Fe3O4 (iron oxide) core and gold as the coating shell. In the preparation of such core-shell metal nanoparticles, two of the biggest issues are attempting to control the rate of coating and controlling the uniformity of the coating to create a solution of nanoparticles which are all of very similar shape and size [43]. Coating of gold or silver onto an iron oxide core can be divided into two main categories: direct coating of gold/silver onto iron [44] or using an intermediary layer to act as a glue between the gold and the iron layer [45]. The former category will be discussed here. The following text describes some methods that have been devised to synthesize gold- and silver-coated Fe3O4 nanoparticles.

Reverse Micelle Synthesis

A popular route for synthesizing metal nanoparticles is to use the reverse micelle method, or sometimes called the microemulsion route [46]. This method was first introduced in the 1980s when colloidal solutions of rhodium, platinum, and palladium nanoparticles were first synthesized [47].

Micelles are formed when molecules with hydrophobic and hydrophilic constituent parts come into contact with either an aqueous or hydrophobic phase [48]. The micelles will organize themselves in such a way that allows the hydrophilic part to be in contact with the aqueous phase and the hydrophobic constituent facing the hydrophobic phase [49]. In essence, a spheroid is formed with an inner shielded phase, which can furthermore contain a cargo [43, 50,51,52].

There are different approaches to the microemulsion route and these include water-in-oil (w/o) [53] and water-in-supercritical CO2 (w/sc-CO2) [54]. A w/o emulsion occurs when water is dispersed in a hydrocarbon-based continuous phase [53], thermodynamically driven surfactant self-assembly, and then generates the reverse micelles, with spherical micelles being the most common shape [43]. Any added polar or ionic materials added to this mixture become compartmentalized within the micelles, and nanoparticles are then formed when the micelle membranes come into contract with each other through Brownian motion [55]. A w/sc-CO2 emulsion involves using a fluid (CO2) that is in a supercritical state, i.e., above both its critical pressure and temperature [56]. This method holds particular interest as it is a more “green” approach to nanoparticle synthesis as no toxic organic solvents are required. It is also easier to recoup the product by simply lowering the pressure and releasing the fluid as CO2 gas [57].

The reverse micelle route has been adapted from synthesizing metal nanoparticles to coating previously synthesized nanoparticles [58]. The first gold-coated iron oxide (Au-Fe3O4) nanoparticles synthesized in reverse micelles were done so almost 20 years ago [59]. This synthesis of Au-Fe3O4 nanoparticles was done using a H2O/CTAB (cetyltrimethyl ammoniumbromide) system to produce the micelles with sodium borohydride (NaBH4) as the reducing agent, reducing gold chloride (HAuCl4) onto the iron core. This synthesis produced a nanoparticle dispersion with an average size of 12 nm. Since this is the first production of Au-Fe3O4 NPs using microemulsions, there has been a range of Au-Fe3O4 NPs synthesis routes discovered [46, 60,61,62,63]. Figure 2 is a generic representation of how the nanoparticles are formed using the reverse micelle route.

Fig. 2
figure 2

A generic representation of the interaction of reverse micelles containing salts the react to form metal nanoparticles

Lin et al. published a slightly modified method to coat Fe3O4 with gold using a reverse micelle method [60]. The synthesis also employs a system using CTAB as the surfactant to form the reverse micelle, but with 1-butanol as a co-surfactant and octane as the oil phase, adding a water solution containing the metal ions using NaBH4 to reduce HAuCl4 onto the surface of the iron oxide nanoparticles. The reported optical results of the coated particles showed a shift in the absorbance peak of the UV/vis spectra from the gold colloid (526 nm) to the Au-Fe3O4 (555 nm). The TEM results of the coated particles indicated a size distribution of 5–15 nm, with an average size of 10 nm. This method was repeated by Pana et al. with a slightly larger size distribution of 5–35-nm-sized Au-Fe3O4 nanoparticles [63]. In addition, a very similar system has been employed by Seip et al. with the exception of using hydrazine to reduce the HAuCl4 [64].

The coating of Fe3O4 nanoparticles is not limited to just gold; Lopez Perez et al. reported on the synthesis of iron oxide nanoparticles using a system containing cyclohexane/Brij-97 (co-surfactant) and an aqueous phase with iron salts of FeSO4.7H2O and FeCl3.6H2O [65]. This system has been coated with both silver [58] and gold [46], producing 13-nm particles. An alternative method is reported by Tamer et al. for the synthesis of Au-Fe3O4 nanoparticles [62]. This method employs a co-precipitation of iron salts in NaOH, which were then washed in HClO4 to produce oxidized Fe3O4 nanoparticles. Coating of gold onto the Fe3O4 NPs occurred via the reduction of HAuCl4 by NaOH delivered to the system by CTAB micelles. Au-Fe3O4 NPs were produced with an average size of 23.5 nm. After characterization, particles were then modified with various functional groups to form a self-assembled monolayer (SAM) and further used for the capturing and detection of Escherichia coli.

A modified version of the reverse micelle synthesis has been done by Zhang et al. involving the use of a laser as the initiator for the coating of iron nanoparticles with gold [66]. The process involves making a reaction mixture of iron nanoparticles encapsulated in CTAB micelles, gold nanopowder in water, and octane, then irradiating with a pulsed laser while vigorously stirring the reaction. The laser irradiation facilitates the thermal decomposition of the gold nanoparticles. Gold atoms and clusters formed around the iron nanoparticles, forming gold-coated iron nanoparticles. The TEM results for the Au-Fe nanoparticles synthesized this way gave an average size of 18 nm with a size distribution of ±36 nm.

Thermal Synthesis

Among the various methods of gold shell-iron core nanoparticle synthesis lies a thermal route, wherein the reaction involves heating the reaction mixture to above its boiling point [67], and sometimes refluxing [68, 69]. There are two main categories for this type of synthesis: hydrothermal (water-based solvent) [70, 71] and solvothermal (organic-based solvent) [68, 72]. While there are many techniques for synthesizing metal nanoparticles via the thermal route [73,74,75,76,77,78], it is not possible to achieve the synthesis of the cores and coating of gold in a one pot reaction [68, 69, 72, 74, 77, 79,80,81], and in some cases, Fe3O4 cores are synthesized via a reverse micelle route [70] or a colloidal route [78] and then the particles are coated using a hydro- or solvothermal technique [70, 76, 78]. While there are a variety of solvent systems that are used in these synthetic methods, the majority of routes involve the addition of either iron oxide nanoparticles to boiling HAuCl4 or the inverse of HAuCl4 being added to boiling solutions of iron oxide nanoparticles [74, 79].

A method for the synthesis of Au-Fe3O4 nanoparticles has been done by Rudakovskaya et al. via a hydrothermal technique [76]. The principle of the method follows the addition of Fe3O4 nanoparticles to a boiling HAuCl4 solution. TEM analysis of these nanoparticles indicated an average size of 30 nm, with a general spherical shape and a size distribution between 20 and 35 nm; these images can be seen in Fig. 3.

Fig. 3
figure 3

A TEM image of the nanoparticles synthesized by Rudakovskaya et al. As can be seen, the nanoparticles are roughly spherically shaped with an average size of 30 nm [76]

Colloidal Synthesis

Colloidal synthesis techniques offer a simple yet effective way of synthesizing metal nanoparticles [82]. Colloidal techniques often offer a level of simplicity over other techniques for nanoparticle synthesis, without the need for different solvents, or that it can be carried out at room temperature [83, 84]. The basic principles of the synthesis involve dispersing different metal ions in an aqueous phase, adding a reducing agent to the mixture, then mixing at a controlled temperature to form insoluble nanoparticles [39]. Colloidal synthesis routes offer the benefit of not having to involve potential toxic solvents in the synthesis (ideal if the nanoparticles are intended for biological use). However, there are some limitations to colloidal routes such as it can be hard to control the size distribution of the final synthesized nanoparticles [85] and the shape of the nanoparticles can be heavily influenced by reagent concentration [85]. On the positive side, it can however be easier to produce nanoparticles in a larger quantity [86]. This method for metal nanoparticle synthesis has been around for many years, being used for the synthesis of different types of nanoparticles such as silver [87] and gold [39, 88].

This basic method has been advanced and developed to produce different synthetic routes for the formation of gold-coated iron oxide nanoparticles [83, 84, 89,90,91,92,93,94,95,96,97]. Most of the methods for the synthesis of gold-coated iron oxide revolve around using various reducing agents to reduce HAuCl4 onto the surface of the iron oxide. Nadagouda et al. offer a proposed “green” synthetic route, using ascorbic acid to reduce HAuCl4 [84]. This method however seems to show little to no control over size or shape of the coated nanoparticles due to the lack of capping agent (an agent that binds to the outside of the nanoparticle that stops further “growth” of the nanoparticle) used in the synthesis [98]. A method which does show more control over the shape and size of synthesized coated particles is presented by Pal et al. [95] This method employs gold acetate as the gold salt, which is reduced onto the surface of 6-nm Fe3O4 nanoparticles to create 7-nm-sized Au–Fe3O4 particles, which are spherical in shape. A rapid method for coating Fe3O4 nanoparticles is presented by Rawal et al. which involves dispersing Fe3O4 nanoparticles in a solution of HAuCl4, then mixing with ethanol [83]. After 15 min at room temperature, the reaction was stopped and the Au-Fe3O4 nanoparticles were then separated with a magnet. TEM analysis of the purified solution showed that the particles produced ranged in size from 30 to 100 nm and had varied shapes across the sample; these images can be seen in Fig. 4. While this synthesis technique produced the coated nanoparticles quickly, it does not appear to be a very efficient synthesis for production of uniformly shaped and sized particles [83].

Fig. 4
figure 4

A TEM image of the nanoparticles synthesized by Rawal et al. These nanoparticles have a size distribution of 20–100 nm [83]

While some techniques offer just the reduction of gold salts, others prefer to put the reducing agent onto the surface of the iron, such as hydroxylamine [90, 93]. In many cases when Fe3O4 nanoparticles are coated with gold, the reduction of a gold salt yields standard gold nanoparticles as well [74], so the addition of the reducing agent onto the surface of the iron nanoparticles aims to improve the efficiency of the coating and is intended to lower the quantity of gold nanoparticles produced as a by-product [93].

Another technique involves seeding gold onto the surface of magnetic nanoparticles which provides a more direct route of getting gold to nucleate around the magnetic core of the nanoparticles [91, 92, 97]. This technique involves binding gold seeds, which are smaller than the iron oxide nanoparticles in solution, to the surface of the iron oxide. When the HAuCl4 is reduced in solution, the Au+ ions will seed onto the iron oxide and form a shell around the iron oxide nanoparticles. This gold seeding has been successfully employed by several groups; Goon et al. used polyethyleneimine to control the seeding of gold onto the surface of Fe3O4, producing fully coated nanoparticles. [91] However, the synthesized Au-Fe3O4 particles displayed high polydispersity, with particle size ranging from 40 to 110 nm. Levin et al. managed to produce gold shell-magnetic core nanoparticles with a size range of 50–70 nm, using a core functionalized with organosilane molecules to bind to the gold seeds [92]. Seeding of gold nanoparticles onto an iron core can be demonstrated with a variety of core shapes, for example, Wang et al. demonstrated gold seeding onto rice-shaped “Nano rice” Fe3O4 structures, which then led to a complete thick gold shell when gold was reduced onto the surface [97].

Bio-Medical Applications of Metal Nanoparticles

Antimicrobial Agents

Bacterial infections are very common, with antibiotics being a primary method of treatment since the discovery of penicillin in 1928 by Alexander Fleming [99]. Nanomedicine provides us with a new, broad range of possible treatment modalities, with metal nanoparticles being explored for future treatments [100]. Table 1 lists some of the nanoparticles that have been explored for antimicrobial applications. One material that has been examined for its potential use is silver, which has shown to have a variety of biomedical uses [101], for example, Sreekumar et al. utilized silver nanoparticles as part of a network of antimicrobial fibers. The nanoparticles varied in size from 20 to 120 nm, with an antibacterial efficacy against Escherichia coli as high as 94.3% compared to the fibers without silver nanoparticles [102]. While it has been shown that an antibiotic such as ampicillin is capable at achieving a kill rate of ≤ 99.9% in E. coli [103], the same study also reported the emergence of resistance to ampicillin in certain strains of E. coli. On this same note, it has been reported that E. coli can develop a resistance to silver nanoparticles; however, this resistance is not a genetic change, but it is a physical response that attempts to cause the colloidal nanoparticles to aggregate [104]. Also employing silver for its antibacterial properties, Holtz et al. designed a system of 60-nm silver vanadate nanowires ‘decorated’ with silver nanoparticles with a diameter of 1–20 nm [105]. This system showed to be promising against three Staphylococcus aureus strains and also interestingly had a much lower growth inhibiting concentration against methicillin-resistant Staphylococcus aureus (MRSA) than the antibiotic oxacillin.

Table 1 List of antibacterial properties that have been exhibited by some metal nanoparticles and metal nanoparticle conjugates

A silver nanoparticle synthesis was reported by Verma et al. where they employed their nanoparticles against the bacteria: Pseudomonas fluorescens, E. coli, and the fungus Candida albicans [106]. The silver nanoparticles had an average minimum inhibitory growth concentration of 5.83 μg/ml across the three strains, compared to some commonly used antibiotics such as ampicillin and neomycin which have minimum inhibitory growth concentrations of 4.0 μg/ml and 16.0 μg/ml, respectively, against strains of E. coli [110]. Of potential interest is the properties the nanoparticles displayed against P. fluorescens an C. albicans, both of which are associated with causing disease in immunocompromised patients [111]. Further investigations might find that the silver nanoparticles are a more efficient way to treat the pathogens than some of the most commonly used antibiotics, such as amphotericin B, which has extensive side effects [112].

The synthesis of thioguanine-capped gold nanoparticles has been reported by Selvaraj et al. where an enhanced antimicrobial effect against several bacterium, including: E. coli, Aspergillus fumigatus, and Pseudomonas aeruginosa [107]. It was found that the thioguanine-capped gold nanoparticles were more effective than unconjugated thioguanine as anticancer and antimicrobial agents, with their activities showing potential use as carriers for cancer drugs. In a similar manner, gold nanoparticles have been reported to have an antimicrobial effect on Corynebacterium pseudotuberculosis [108], nanoparticles with an average size of 25 nm, using a dose of 50 μg/ml showed a bacterial growth inhibition of 95% after 20 min of exposure. Similarly, naked gold nanoparticles were shown to have an antimicrobial effect on a variety of gram negative and gram positive bacteria including S. aureus, Klebsiella pneumonia, and Bacillus subtilis [109]. A dose of 1.35 μg/ml of AuNPs showed a growth inhibition of 46.4±0.4%, 38.3±0.2%, and 57.8±0.2% for S. aureus, K. pneumonia, and B. subtilis, respectively.


As with antibacterial applications, metal nanoparticles have shown to be promising in antiviral applications; Table 2 demonstrates a range of nanoparticles that have been shown to possess antiviral properties and could potentially be applied when treating viruses. Both naked and coated silver nanoparticles [113,114,115,116] have been shown to have a range of antiviral applications when in the nano-scale range.

Table 2 Some of the metal nanoparticles and metal nanoparticle conjugates that have been demonstrated as having antiviral properties

Hepatitis B (HBV) is a viral infection that currently affects 257 million people around the world and was responsible for 887,000 deaths in 2015 according to the World Health Organization [121]. Small (10–50 nm) naked silver nanoparticles have been tested as a possible treatment for HBV [113] and were shown to bind efficiently to HBV and further inhibit the production of HBV RNA. The mode of action is hypothesized to be due to the AgNPs binding to the HBV dsDNA (double-stranded DNA). Rogers et al. have demonstrated a use for silver nanoparticles, both naked and with a polysaccharide coating as an antiviral agent against monkeypox virus (MPV) [114]. The nanoparticles were tested in vitro against MPV at a range of concentrations between 12.5–100 μg/ml; the results of the study showed that all of the concentrations of polysaccharide-coated silver nanoparticles (Ag-PS-NPs) used were able to reduce MPV-induced plaque formations in vitro.

Silver nanoparticles may even have a role to play in the treatment of human immunodeficiency virus (HIV) [115, 116]. HIV is a major health concern, with WHO estimating that 36.7 million people are living with HIV as of 2016 [122]. It is important that treatments for HIV are discovered and implemented quickly and efficiently; Lara et al. have demonstrated the effect of silver nanoparticles (30–50 nm) on HIV-1 isolates showing inhibition of all strains of HIV-1 isolates [116]. The naked nanoparticles showed an overall IC50 of 0.44 mg/ml ± 0.3 against HIV-1, with the mechanism of viral inhibition shown to be the inhibition of virus-host cell binding, specifically the silver nanoparticles inhibit the interaction between the gp120 protein (an envelope glycoprotein) and the target cell membrane receptors. Also demonstrated by the same group was the ability for silver nanoparticles coated with polyvinylpyrrolidone (PVP) to prevent the transfection of HIV-1 into a human cervical tissue explant model [115]. Specifically, 0.15 mg/ml PVP-coated silver nanoparticles (PVP-AgNPs) inhibited infection by HIV-IIIB and HIV-AZT-RV isolates. This concentration of PVP-AgNPs also induced a proliferation of lymphocytes (immune cells) to the site of infection, in comparison to the control sample [115].

It is not only silver and coated silver nanoparticles that have been employed against viruses: 2-nm gold nanoparticles coated with an amphiphilic sulfate ligand were also shown to be effective against HIV-1 [118]. These particles were shown to target the fusion process of the virus and were shown in vitro to bind to gp120 protein and directly neutralize the HIV-1 infection. Mercaptoethanesulfonate-coated gold nanoparticles (Au-MES) showed an inhibition of herpes simplex virus type 1 (HSV-1) infection, possibly by inhibiting the virus binding to the host cell, cell to cell viral spreading, or alteration of cell susceptibility to viral infection induced by the presence of the nanoparticles [117].

Copper-iodide nanoparticles (CuI-NPs) have been shown to have antiviral properties on several different viruses: feline calicivirus (FCV) [119] and more interestingly influenza A virus of swine origin (H1N1) [120]. One hundred to 400 nm CuI-NPs showed an antiviral property when utilized against FCV, and it was hypothesized that monovalent Cu ions were responsible for the production of a reactive oxygen species (ROS) that caused subsequent capsid protein oxidation, leading to FCV inactivation. H1N1 virus was also shown to be inhibited by CuI-NPs, in a very similar manner, namely the production of hydroxyl radicals, leading to protein degradation. However, these radicals might also prove to be toxic to non-infected tissues, which would be important to determine before a treatment would be approved for use [123].


Magnetic resonance imaging (MRI) scanning is a very useful tool for medical diagnosis and provides clear anatomical images. Using MRI, one can visualize the blood flow, physiochemical traits, and the states of tissues and organs in the body [124]. Contrast agents are often employed in MRI for improved diagnostic sensitivity [125]. Conventionally used contrast agents are chelate-based, but the major drawbacks of current contrast agents are their biological stability and their toxicity levels when accumulated in cells [126]. For example, some contrast agents are iodine-based, and it has been reported that iodinated contrast media exposure is associated with subsequent development of incident hyperthyroidism and incident overt hypothyroidism [127]. Alternatives have been developed to provide an improved scanning efficacy by reducing the negative impact contrast agents can have on the body [128]. Alternatives include metal nanoparticles possibly conjugated with an agent which acts in a similar manner to a contrast agent for MRI scanning [129]. Figure 5 is an MRI contrast image of a rat cerebral cortex pre- and post-treatment of AuNPs [130].

Fig. 5
figure 5

An MRI contrast image of a rat cerebral cortex pre- (left) and post-treatment (right). The area containing the AuNPs is ringed in red

Table 3 shows some of the nanoparticles that have been explored for use in medical imaging. Some computed tomography (CT) contrast agents have issues including short circulation half-lives [131] and potential tissue damage [130]. Due to this, metal nanoparticles have also been investigated for use in CT imaging [132]; Au nanoparticles show promising use in imaging due to their X-ray attenuation [133]. Kojima et al. showed that gold nanoparticles conjugated with a PEGylated dendrimer (PEG-AuNPs) made for a superior contrast agent in vitro as well as for X-ray computed tomography, compared to the commercially available iodine agent iopamidal [134]. The PEG-AuNPs showed a higher contrast efficiency than the commercially available iopamidal, with rapid excretion from the body [135]. The authors also noted that the PEG-AuNPs had photocytotoxic properties to enable photothermal therapy.

Table 3 Some examples of metal nanoparticles and metal nanoparticle-conjugates that have been investigated for their use in medical imaging

Li et al. have demonstrated the use of coated AuNPs as an imaging tool for atherosclerosis; the AuNPs were applied in a type of medical imaging called “single-photon emission computed tomography” (SPECT) [136]. This type of imaging is very similar to using a gamma camera, but it is able to provide true 3D images that can be sliced, rotated, and manipulated to achieve a more accurate analytical technique [136]. The modified nanoparticles specifically targeted atherosclerosis plaques containing apoptotic macrophages, indicating a useful tool for invasively accurate detection of atherosclerosis plaques [136].

AuNPs have previously been demonstrated to be a possible agent for photoacoustic imaging (PA), showing high spatial resolution and sensitivity [137]. PA relies on the detection of ultrasonic waves which are emitted from tissues when exposed to non-ionizing pulsed laser irradiation [140]. The intensity/magnitude of the ultrasonic emission is responsible for the image contrast, therefore any agent that can both absorb the laser pulses and then give off heat as a result will increase the magnitude of the ultrasonic emission and AuNPs possess the ability to do both of these [141, 142]. AuNPs are potentially better than organic dyes due to the organic dyes’ susceptibility to photo-bleaching and rapid clearing from the blood [143]. AuNPs also have use in cell imaging for examining movement of nanoparticles within cells when conjugated with various cargoes. Figure 6 is a darkfield imaging of A431 lung cancer cells treated with AuNPs that target epidermal growth factor receptor, and the bright areas within the cells are the nanoparticles indicating their locations within the cells [144].

Fig. 6
figure 6

Darkfield imaging of A431 lung cancer cells treated with AuNPs; the bright yellow/orange dots are nanoparticles within the cells

Biomedical Cargo Delivery

Nanoparticles make for an ideal molecule for drug delivery due to the huge surface area to the volume ratio they provide when compared to their bulk material [145]. In addition, it is possible to engineer nanoparticles to either avoid or interact with the immune system in specific ways [146, 147]. For example, it has been demonstrated that an increased hydrophobicity of nanoparticles/sub-groups conjugated to the nanoparticles illicit and increased immune response by measuring cytokine mRNA levels in mice [146]. Focusing in the opposite direction, it has been suggested that nanoparticles can be conjugated with various ligands to directly activate the immune system to target the destruction of a tumor [148] or by accumulation in the liver or spleen for the generation of tolerance or immunity, respectively [147].

Gold nanoparticles have been extensively studied for their delivery of medical cargo, for example, Bhumkar et al. have explored the application of AuNPs for trans-mucosal delivery of insulin. Gold nanoparticles were synthesized in the presence of chitosan, which acts as a polymeric stabilizer [149]. These nanoparticles were then loaded with insulin and administered both nasally and orally to diabetic rats. The results showed an overall reduction in the rat’s blood glucose levels, an indication of successful movement of the nanoparticles through the mucosal membranes and into the bloodstream.

More recently “smart” AuNPs have been employed in PA [138]. These nanoparticles are roughly 10 nm in diameter and are functionalized with citraconic amide moieties which are susceptible to hydrolysis. The citraconic amides are converted into positively charged primary amino acids at a mildly acidic pH, while the surface molecules adopt negative charges at physiological pH [138]. Combined, these two properties cause the “smart” nanoparticles to adopt both positive and negative charges allowing them to aggregate rapidly due to electrostatic attraction. These nanoparticles are referred to as “smart” due to the nanoparticles presenting cancer-specific properties and accumulate rapidly and efficiently in cancer tissues and show a much lower accumulation in normal tissues [150].

Gold nanoparticles can also be used as a delivery system for nucleic acids [153], including oligonucleotides [151] and small interfering RNA (siRNA) [154]. Many different methods have been developed to functionalize AuNPs with nucleic acids, for example, Yonezawa et al. have synthesized gold nanoparticles modified with thiocholine, which then bound to DNA and formed a fusion of wire-like structures throughout the DNA [155]. Sandström et al. demonstrated the ability to bind nucleic acids onto gold nanoparticles [151], and a similar modification has been done by Rosi et al. where tetrathiol-modified antisense oligonucleotides were bound to 13-nm gold nanoparticles [152]. Being able to conjugate nucleic acids to nanoparticles opens up the possibility of targeted gene delivery, which could, for example, lead to genes coding for a specific protein to be delivered to a cell that was either deficient in that protein or could not produce the protein themselves [156]. It has also been exhibited that gold nanoparticles modified with DNA can transfect cancer cells [157] (Table 4).

Table 4 A range of nanoparticle conjugates that have been examined for medical delivery of cargos

Anticancer Drug Delivery

Cancer is one of the world’s leading killers with large areas of scientific research being dedicated to the fight against cancer, and nanoparticles offer a new doorway into methods to target and treat cancer. Table 5 presents a selection of nanoparticle/drug conjugates that have been tested for anticancer treatments. Paciotti et al. have investigated the application of PEGylated AuNPs as a carrier for tumor necrosis factor (TNF) which is a cell-signaling protein that possess the ability to induce apoptosis in healthy cells [158]. The Au-PEG-TNF nanoparticles were injected intravenously and agglomerated significantly more in MC-38 colon carcinoma cells compared to other healthy cells/tissues. The TNF not only gave therapeutic action on the MC-38 cells, but also seemed to possess a targeting property, indicated by the lack of agglomeration in healthy cells. Another interesting observation reported was the ability for the Au-PEG-TNF nanoparticles to diminish a tumor mass compared to “free” TNF.

Table 5 A range of nanoparticle conjugates that have been examined for anticancer therapy

Doxorubicin is a widely used cancer therapeutic agent but has dose-limiting associations with cardiotoxicity. A gold nanoparticle-doxorubicin conjugate has been developed that demonstrates little no to cardiotoxicity to mice while being able to treat cancer [160]. Dixit et al. demonstrated the selective delivery of folic acid-coated AuNPs into folate receptor (FR) positive cancer cells, whereas when compared with a cell line that did not have folate receptors, uptake was shown to be minimal [159]. These results demonstrated the use of folate to target metal nanoparticles to FR-positive cancer cells for tumor imaging and ablation.

Limitations of Single Metal Nanoparticles and Overcoming Them

The principal obstacle with nanoparticle drug delivery is the ability to direct the nanoparticle to the target area [162, 163]. There are several methods in use for metal nanoparticle targeting such as antibodies [164,165,166] and homing peptides [167, 168]. There are however limitations to these methods, with the biggest being that before they even reach the desired target cells they have to pass through a variety of other barriers, such as blood vessels and the blood-brain barrier [169]. One way to overcome this targeting limitation is to use magnetic nanoparticles [170]. A magnetic nanoparticle-targeting system works by directing the nanoparticles to a target site using an external magnetic field, it has already been demonstrated that the magnetic anisotropy of the nanoparticle is a very important factor for medical treatments [171], with a change in anisotropy being able to the change the efficacy of hypothermia treatments for example [172]. Superparamagnetic metal nanoparticles have this property (they only present magnetic properties while in the presence of a magnetic field) [173]. However, the benefit of magnetic nanoparticles also presents a potential limitation, due to the toxicity of many magnetic materials [31, 174, 175]. Despite iron being approved for various imaging uses [5, 6, 31], it has been suggested in several studies that naked iron oxide nanoparticles may have some adverse effects when used in cell labeling [176,177,178]. One method that can be used to overcome any potential toxicity limitations is to coat the iron core [179]. A range of materials can be used as the coating material: silica [180,181,182], polymers [183, 184], gold [62, 93, 95, 185], or silver [58, 186]. Gold has low pharmaceutical activity [187] and silver has been used in biomedical applications for many years [188, 189],

The combination of a superparamagnetic core with an inert and safe metal coating produces metal nanoparticles with superior characteristics to non-magnetic metal particles [190]. As well as reducing toxicity, the coating also provides the potential for the conjugation of functionalized molecules onto the surface, such as drugs and biomolecules for application in the medical field [97, 140, 152]. It is of note that a core-shell nanoparticle still possesses the properties and uses of a nanoparticle made from the same material as just the shell, but the superparamagnetic core gives the ability to direct the nanoparticle in the body [191]. For example, a gold nanoparticle with an antibody is classified as a targeting nanoparticle, introducing the core would classify the nanoparticle as a directed targeting nanoparticle [173].

Current Medicinal Uses of Gold-Coated Iron Oxide Nanoparticles

Core-shell superparamagnetic nanoparticles have already been assessed for their biomedical uses, with a wide range of uses already being applied [192] and with a majority of research investigating into the use of gold as a shell for the nanoparticles, in part due to its biocompatibility and ability to easily bind to a variety of materials. As such, this section will deal exclusively with gold shell nanoparticles. One of these uses is as a magnetic carrier for drug targeting [192,193,194,195,196]. Kayal and Ramanujan have tested an in vitro apparatus that simulates the human circulatory system as a test for the magnetic delivery of gold-coated iron oxide nanoparticles (Au-Fe3O4) loaded with doxorubicin [194]. Their system had various magnetic fields of increasing strength next to a capillary through which the doxorubicin-loaded particles were passed. A significant percentage of these nanoparticles were captured within the magnetic fields, strongly indicating the potential for the use of magnetic nanoparticles in drug delivery. Another use for a targeted system is the application of Au-Fe3O4 nanoparticles in photothermal therapy. Bhana et al. demonstrated the use of a core-shell system used in combination therapy deployed against two different cancer cell lines; head and neck (KB-3-1) and breast (SK-BR-3) with a reported decrease in cell viability of 64% when they exposed cell lines to a combined photothermal and photodynamic therapy, compared to each modality used on its own [197]. In photothermal therapy, gold nanoparticles are coated with a ligand, such as PEG [142], and these nanoparticles are irradiated with a laser, with a wavelength that matches the UV-vis λ-max of the gold nanoparticles [194]. The nanoparticles vibrate at the laser’s frequency which causes heat to be released causing the death of the surrounding tissue [198], introducing a core which is superparamagnetic can allow for a more accurate targeting for use in this therapy. Similarly, it has been reported by Kirui et al. that gold hybrid nanoparticles were deployed against SW1222 colorectal cancer in photothermal therapy, showing an increased case of cellular apoptosis after therapy, with their conclusion being that the cells showed an increased uptake, leading to a reduced laser power required to reach threshold therapeutic levels [199]. The use of core-shell nanoparticles for photothermal therapy of cancer has also been reported by other groups [200, 201].

Metal nanoparticles have already shown to have a place in contrast imaging, for example core-shell nanoparticles can also be used in T1- and T2-weighted imaging in MRI [202]. Research by Cho et al. demonstrated that gold-coated iron nanoparticles can be successfully used in MRI imaging, as well as opening the route for conjugating various ligands for use in biosensors [202]. A magnetic carrier capable of imaging and photothermal therapy has been reported by Cheng et al. They demonstrated the magnetic targeting of multi-functional nanoparticles to a tumor in a mouse model, which could be imaged inside the tumor and showed a reduction in the tumor size when combined with photothermal therapy [203]. It is also of note that in this work, both the nanoparticle dosage (1.6 mg/kg) and laser power (1 W/cm2) are among the lowest applied for in vivo photothermal therapy. Moreover, there was no obvious toxicity from the nanoparticles reported. Table 6 presents some of the currently reported uses of core-shell nanoparticles.

Table 6 Examples of the medical uses already been demonstrated for gold-coated iron magnetic nanoparticles

Another medical area where such core-shell metal nanoparticles have been suggested to make an impact is in directed enzyme prodrug therapy (DEPT) [170, 191]. DEPT is a promising method of cancer treatment, with several therapies making it through to clinical trials [207, 208]. The main principal of DEPT is the targeted delivery of a prodrug-activating enzyme to a tumor site. Upon arrival at the tumor site, the enzyme enters the target cells where it can later activate an administered prodrug. However, the efficacy of the therapy depends on the ability to direct the enzyme to the tumor site, with current directional techniques relying on passive targeting methods such as viruses [207, 209] or antibodies [210, 211], rather than an active targeting system for enzyme delivery. A novel therapy proposed by Gwenin et al. potentially overcomes the targeting issue [170, 212]. This approach involves conjugating a genetically modified prodrug-activating enzyme onto the surface of a gold-coated iron oxide superparamagnetic nanoparticle (AuMNP), then directing the AuMNP-enzyme conjugate to the target site using a magnetic field to increase the efficacy of the targeted therapy. Figure 7 presents some of the uses of a core-shell nanoparticle.

Fig. 7
figure 7

A pictorial representation of the applications of core/shell nanoparticles


In brief, single metal nanoparticles have been shown to currently possess a wide range of biomedical applications, with more application for these nanoparticles being discovered. One of the limiting factors that these nanoparticles face in medical treatments is to find a way for precise accurate targeting of areas within the body, be it for targeting of a drug delivery or for therapies involving the nanoparticles directly. A way to overcome this is to employ a magnetic core to create core-shell nanoparticles that can then be directed around a body using a magnetic field. There are a variety of methods that can be used to synthesize these core-shell nanoparticles, with each method having its own advantages and disadvantages. There remain many obstacles for core-shell nanoparticles before they can be routinely applied in the medical field and these include

  1. 1)

    Achieving a synthesis route which produces easily repeatable results;

  2. 2)

    Producing particles of a set size [22,23,24] and shape [25,26,27,28]; and

  3. 3)

    Producing large enough quantities to make it economically viable [29].

Another key factor is the relatively unknown toxicity of some nanoparticles over an extended period of time due to how relatively new the field of research is.

Availability of Data and Materials

Not applicable







Water-in-supercritical CO2


Silver nanoparticle


Polysaccharide-coated silver nanoparticles

Au-Fe3O4 :

Gold-coated iron oxide nanoparticle


Mercaptoethane sulfate-coated gold nanoparticle


Gold nanoparticle


Polyethylene glycol-coated tumor necrosis factor-loaded gold nanoparticles


Computed tomography


Cetyltrimethylammonium bromide

CuI NPs:

Copper-iodine nanoparticles


Deoxyribonucleic acid


Feline calicivirus


Folate receptor


Glycoprotein 120


Influenza A of swine origin


Hepatitis B virus


Human immune-deficiency virus-1


Herpes simplex virus 1


Head and neck cancer


Colon carcinoma


Monkeypox virus


Magnetic resonance imaging


Photoacoustic imaging


Polyethylene glycol


Polyvinylpyrrolidone-coated silver nanoparticle


Ribonucleic acid


Reactive oxygen species


Small interfering ribonucleic acid


Breast cancer


Single-photon emission computed tomography


Tumor necrosis factor


  1. 1.

    Hofmann-Amtenbrink M, Grainger DW, Hofmann H (2015) Nanoparticles in medicine: current challenges facing inorganic nanoparticle toxicity assessments and standardizations. Nanomedicine 11:1689–1694

    CAS  Article  Google Scholar 

  2. 2.

    Gao X, Cui Y, Levenson RM et al (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22:969–976

    CAS  Article  Google Scholar 

  3. 3.

    Akerman ME, Chan WCW, Laakkonen P et al (2002) Nanocrystal targeting in vivo. Proc Natl Acad Sci 99:12617–12621

    CAS  Article  Google Scholar 

  4. 4.

    Kim S, Lim YT, Soltesz EG et al (2004) Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 22:93–97

    CAS  Article  Google Scholar 

  5. 5.

    Harisinghani MG, Barentsz J, Hahn PF et al (2003) Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 348:2491–2499

    Article  Google Scholar 

  6. 6.

    Huh Y-M, Jun Y, Song H-T et al (2005) In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals. J Am Chem Soc 127:12387–12391

    CAS  Article  Google Scholar 

  7. 7.

    Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2:347–360

    CAS  Article  Google Scholar 

  8. 8.

    Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303:1818–1822

    CAS  Article  Google Scholar 

  9. 9.

    Micha JP, Goldstein BH, Birk CL et al (2006) Abraxane in the treatment of ovarian cancer: the absence of hypersensitivity reactions. Gynecol Oncol 100:437–438

    CAS  Article  Google Scholar 

  10. 10.

    Sengupta S, Eavarone D, Capila I et al (2005) Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature 436:568–572

    CAS  Article  Google Scholar 

  11. 11.

    Garcia-Garcia E, Andrieux K, Gil S, Couvreur P (2005) Colloidal carriers and blood-brain barrier (BBB) translocation: a way to deliver drugs to the brain? Int J Pharm 298:274–292

    CAS  Article  Google Scholar 

  12. 12.

    Schlachetzki F, Zhang Y, Boado RJ, Pardridge WM (2004) Gene therapy of the brain: the trans-vascular approach. Neurology 62:1275–1281

    CAS  Article  Google Scholar 

  13. 13.

    Popovic N, Brundin P (2006) Therapeutic potential of controlled drug delivery systems in neurodegenerative diseases. Int J Pharm 314:120–126

    CAS  Article  Google Scholar 

  14. 14.

    Olbrich C, Bakowsky U, Lehr CM et al (2001) Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA. J Control Release 77:345–355

    CAS  Article  Google Scholar 

  15. 15.

    Tabatt K, Sameti M, Olbrich C et al (2004) Effect of cationic lipid and matrix lipid composition on solid lipid nanoparticle-mediated gene transfer. Eur J Pharm Biopharm 57:155–162

    CAS  Article  Google Scholar 

  16. 16.

    De Jaeghere F, Allémann E, Kubel F et al (2000) Oral bioavailability of a poorly water soluble HIV-1 protease inhibitor incorporated into pH-sensitive particles: effect of the particle size and nutritional state. J Control Release 68:291–298

    Article  Google Scholar 

  17. 17.

    Pignatello R, Bucolo C, Spedalieri G et al (2002) Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application. Biomaterials 23:3247–3255

    CAS  Article  Google Scholar 

  18. 18.

    Pignatello R, Bucolo C, Ferrara P et al (2002) Eudragit RS100® nanosuspensions for the ophthalmic controlled delivery of ibuprofen. Eur J Pharm Sci 16:53–61

    CAS  Article  Google Scholar 

  19. 19.

    Ludwig A (2005) The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev 57:1595–1639

    CAS  Article  Google Scholar 

  20. 20.

    John AE, Lukacs NW, Berlin AA et al (2003) Discovery of a potent nanoparticle P-selectin antagonist with anti-inflammatory effects in allergic airway disease. FASEB J 17:1-12

    CAS  Article  Google Scholar 

  21. 21.

    Kumar M, Xiaoyuan K, Behera AK et al (2003) Chitosan IFN-γ-pDNA nanoparticle (CIN) therapy for allergic asthma. Genet Vaccines Ther 1:1-10

  22. 22.

    Teranishi T, Miyake M (1998) Size control of palladium nanoparticles and their crystal structures. Chem Mater 10:594–600

    CAS  Article  Google Scholar 

  23. 23.

    Sun S, Zeng H (2002) Size-controlled synthesis of magnetite nanoparticles. J Am Chem Soc 124:8204–8205

    CAS  Article  Google Scholar 

  24. 24.

    Pileni M-P (2003) The role of soft colloidal templates in controlling the size and shape of inorganic nanocrystals. Nat Mater 2:145–150

    CAS  Article  Google Scholar 

  25. 25.

    Sun Y, Xia Y (2002) Shape-controlled synthesis of gold and silver nanoparticles. Science 298:2176–2179

    CAS  Article  Google Scholar 

  26. 26.

    Manna L, Scher EC, Alivisatos AP (2000) Synthesis of soluble and processable rod-, arrow-, teardrop-, and tetrapod-shaped CdSe nanocrystals. J Am Chem Soc 122:12700–12706

    CAS  Article  Google Scholar 

  27. 27.

    Gadogbe M, Ansar SM, Chu IW et al (2014) Comparative study of the self-assembly of gold and silver nanoparticles onto thiophene oil. Langmuir 30:11520–11527

    CAS  Article  Google Scholar 

  28. 28.

    Klajn R, Pinchuk AO, Schatz GC, Grzybowski BA (2007) Synthesis of heterodimeric sphere-prism nanostructures via metastable gold supraspheres. Angew Chem Int Ed 46:8363–8367

    CAS  Article  Google Scholar 

  29. 29.

    Wang X, Hall JE, Warren S et al (2007) Synthesis, characterization, and application of novel polymeric nanoparticles. Macromolecules 40:499–508

    CAS  Article  Google Scholar 

  30. 30.

    Mazzola L (2003) Commercializing nanotechnology. Nat Biotechnol 21:1137–1143

    CAS  Article  Google Scholar 

  31. 31.

    Markides H, Rotherham M, El Haj AJ (2012) Biocompatibility and toxicity of magnetic nanoparticles in regenerative medicine. J Nanomater 2012:1–11

    Article  CAS  Google Scholar 

  32. 32.

    Buzea C, Pacheco I (2019) Toxicity of nanoparticles. In: Nanotechnology in eco-efficient construction. Elsevier, pp 705–754

  33. 33.

    Faraji AH, Wipf P (2009) Nanoparticles in cellular drug delivery. Bioorganic Med Chem 17:2950–2962

    CAS  Article  Google Scholar 

  34. 34.

    Liao H, Nehl CL, Hafner JH (2006) Biomedical applications of plasmon resonant metal nanoparticles. Nanomedicine (Lond) 1:201–208

    CAS  Article  Google Scholar 

  35. 35.

    Lanone S, Boczkowski J (2006) Biomedical applications and potential health risks of nanomaterials: molecular mechanisms. Curr Mol Med 6:651–663

    CAS  Article  Google Scholar 

  36. 36.

    Singh R, LJ W (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86:215–223

    CAS  Article  Google Scholar 

  37. 37.

    Kruis FE, Fissan H, Peled A (1998) Synthesis of nanoparticles in the gas phase for electronic, optical and magnetic applications—a review. J Aerosol Sci 29:511–535

    CAS  Article  Google Scholar 

  38. 38.

    Chen M, Yamamuro S, Farrell D, Majetich SA (2003) Gold-coated iron nanoparticles for biomedical applications. J Appl Phys 93:7551–7553

    CAS  Article  Google Scholar 

  39. 39.

    Stevenson PC, Turkevich J, Hillier J (1951) A study of the nucleation and growth processes in the synthesis of. Discuss Faraday Soc 11:55–75

    Article  Google Scholar 

  40. 40.

    Cuenya BR (2010) Synthesis and catalytic properties of metal nanoparticles: size, shape, support, composition, and oxidation state effects. Thin Solid Films 518:3127–3150

    CAS  Article  Google Scholar 

  41. 41.

    Laurent S, Forge D, Port M et al (2008) Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev 108:2064–2110

    CAS  Article  Google Scholar 

  42. 42.

    Ling D, Hyeon T (2013) Chemical design of biocompatible iron oxide nanoparticles for medical applications. Small 9:1450–1466

    CAS  Article  Google Scholar 

  43. 43.

    Eastoe J, Hollamby MJ, Hudson L (2006) Recent advances in nanoparticle synthesis with reversed micelles. Adv Colloid Interf Sci 128–130:5–15

    Article  CAS  Google Scholar 

  44. 44.

    Moraes Silva S, Tavallaie R, Sandiford L et al (2016) Gold coated magnetic nanoparticles: from preparation to surface modification for analytical and biomedical applications. Chem Commun 52:7528–7540

    CAS  Article  Google Scholar 

  45. 45.

    Fang C-L, Qian K, Zhu J et al (2008) Monodisperse α-Fe2O3@ SiO 2@ Au core/shell nanocomposite spheres: synthesis, characterization and properties. Nanotechnology 19:125601

    Article  CAS  Google Scholar 

  46. 46.

    Iglesias-Silva E, Vilas-Vilela JL, López-Quintela MA et al (2010) Synthesis of gold-coated iron oxide nanoparticles. J Non-Cryst Solids 356:1233–1235

    CAS  Article  Google Scholar 

  47. 47.

    Boutonnet M, Kizling J, Stenius P, Maire G (1982) The preparation of monodisperse colloidal metal particles from microemulsions. Colloids Surf 5:209–225

    CAS  Article  Google Scholar 

  48. 48.

    Tanford C (1974) Theory of micelle formation in aqueous solutions. J Phys Chem 78:2469–2479

    CAS  Article  Google Scholar 

  49. 49.

    Pileni MP (1997) Nanosized particles made in colloidal assemblies. Langmuir 13:3266–3276

    CAS  Article  Google Scholar 

  50. 50.

    Holmes JD, P A B, B A K, Johnston KP (1999) Synthesis of cadmium sulfide Q particles in water-in-CO 2 microemulsions. Langmuir 15:6613–6615

    CAS  Article  Google Scholar 

  51. 51.

    Ohde H, Ye X-R, Wai CM, Rodriguez JM (2000) Synthesizing silver halide nanoparticles in supercritical carbon dioxide utilizing a water-in-CO2 microemulsion. Chem Commun 2354:2353–2354

    Article  Google Scholar 

  52. 52.

    Ohde H, Wai CM, Kim H et al (2002) Hydrogenation of olefins in supercritical CO 2 catalyzed by palladium nanoparticles in a water-in-CO 2 microemulsion. J Am Chem Soc 124:4540–4541

    CAS  Article  Google Scholar 

  53. 53.

    Carpenter EE, Seip CT, O’Connor CJ (1999) Magnetism of nanophase metal and metal alloy particles formed in ordered phases. J Appl Phys 85:5184–5186

    CAS  Article  Google Scholar 

  54. 54.

    Lim KT, Hwang HS, Ryoo W, Johnston KP (2004) Synthesis of TiO2 nanoparticles utilizing hydrated reverse micelles in CO2. Langmuir 20:2466–2471

    CAS  Article  Google Scholar 

  55. 55.

    Bommarius AS, Holzwarth JF, Wang DIC, Hatton TA (1990) Coalescence and solubilizate exchange in a cationic four-component reversed micellar system. J Phys Chem 94:7232–7239

    CAS  Article  Google Scholar 

  56. 56.

    Liu J, Raveendran P, Shervani Z et al (2005) Synthesis of Ag and AgI quantum dots in AOT-stabilized water-in-CO 2 microemulsions. Chem A Eur J 11:1854–1860

    CAS  Article  Google Scholar 

  57. 57.

    Liu J, Ikushima Y, Shervani Z (2003) Environmentally benign preparation of metal nano-particles by using water-in-CO2 microemulsions technology. Curr Opin Solid State Mater Sci 7:255–261

    CAS  Article  Google Scholar 

  58. 58.

    Iglesias-Silva E, Rivas J, León Isidro LM, López-Quintela MA (2007) Synthesis of silver-coated magnetite nanoparticles. J Non-Cryst Solids 353:829–831

    CAS  Article  Google Scholar 

  59. 59.

    Carpenter EE, Sangregorio C, Connor CJ (1999) Effects of shell thickness on blocking temperature of nanocomposites of metal particles with gold shells. IEEE Trans Magn 35:3496–3498

    CAS  Article  Google Scholar 

  60. 60.

    Lin J, Zhou W, Kumbhar A et al (2001) Gold-coated Iron (Fe@ Au) nanoparticles: synthesis, characterization, and magnetic field-induced self-assembly. J Solid State Chem 159:26–31

    CAS  Article  Google Scholar 

  61. 61.

    Cho S-J, Idrobo J-C, Olamit J et al (2005) Growth mechanisms and oxidation resistance of gold-coated iron nanoparticles. Chem Mater 17:3181–3186

    CAS  Article  Google Scholar 

  62. 62.

    Tamer U, Cetin D, Suludere Z et al (2013) Gold-coated iron composite nanospheres targeted the detection of Escherichia coli. Int J Mol Sci 14:6223–6240

    CAS  Article  Google Scholar 

  63. 63.

    Pana O, Teodorescu CM, Chauvet O et al (2007) Structure, morphology and magnetic properties of Fe-Au core-shell nanoparticles. Surf Sci 601:4352–4357

    CAS  Article  Google Scholar 

  64. 64.

    Seip CT, O’Connor CJ (1999) Fabrication and organization of self-assembled metallic nanoparticles formed in reverse micelles. Nanostruct Mater 12:183–186

    Article  Google Scholar 

  65. 65.

    Lopez Perez JA, Lopez Quintela MA, Mira J et al (1997) Advances in the preparation of magnetic nanoparticles by the microemulsion method. J Phys Chem B 101:8045–8047

    CAS  Article  Google Scholar 

  66. 66.

    Zhang J, Post M, Veres T et al (2006) Laser-assisted synthesis of superparamagnetic Fe@ Au core-shell nanoparticles. J Phys Chem B 110:7122–7128

    CAS  Article  Google Scholar 

  67. 67.

    Takami S, Sato T, Mousavand T et al (2007) Hydrothermal synthesis of surface-modified iron oxide nanoparticles. Mater Lett 61:4769–4772

    CAS  Article  Google Scholar 

  68. 68.

    Park H-Y, Schadt MJ, Wang L et al (2007) Fabrication of magnetic core@ shell Fe oxide@ Au nanoparticles for interfacial bioactivity and bio-separation. Langmuir 23:9050–9056

    CAS  Article  Google Scholar 

  69. 69.

    Liu HL, Hou P, Zhang WX, Wu JH (2010) Synthesis of monosized core-shell Fe3O4/Au multifunctional nanoparticles by PVP-assisted nanoemulsion process. Colloids Surfaces A Physicochem Eng Asp 356:21–27

    CAS  Article  Google Scholar 

  70. 70.

    Banerjee S, Raja SO, Sardar M et al (2011) Iron oxide nanoparticles coated with gold: enhanced magnetic moment due to interfacial effects. J Appl Phys 109:1-8

    Article  CAS  Google Scholar 

  71. 71.

    Sun X, Zheng C, Zhang F et al (2009) Size-controlled synthesis of magnetite (Fe3O4) nanoparticles coated with glucose and gluconic acid from a single Fe(III) precursor by a sucrose bifunctional hydrothermal method. J Phys Chem C 113:16002–16008

    CAS  Article  Google Scholar 

  72. 72.

    Aneesh PM, Vanaja KA, Jayaraj MK (2007) Synthesis of ZnO nanoparticles by hydrothermal method, vol 6639, p 66390J

    Google Scholar 

  73. 73.

    Brust M, Walker M, Bethell D et al (1994) Synthesis of thiol-derivatised gold nanoparticles in a two-phase liquid–liquid system. J Chem Soc Chem Commun:801–802

    CAS  Article  Google Scholar 

  74. 74.

    Ban Z, Barnakov YA, Li F et al (2005) The synthesis of core–shell iron@ gold nanoparticles and their characterization. J Mater Chem 15:4660

    CAS  Article  Google Scholar 

  75. 75.

    Zhai Y, Zhai J, Wang Y et al (2009) Fabrication of iron oxide core/gold shell submicrometer spheres with nanoscale surface roughness for efficient surface-enhanced Raman scattering. J Phys Chem C 113:7009–7014

    CAS  Article  Google Scholar 

  76. 76.

    Rudakovskaya PG, Beloglazkina EK, Majouga AG, Zyk NV (2010) Synthesis and characterization of terpyridine-type ligand-protected gold-coated Fe3O4 nanoparticles. Mendeleev Commun 20:158–160

    CAS  Article  Google Scholar 

  77. 77.

    Mohammad F, Balaji G, Weber A et al (2010) Influence of gold nanoshell on hyperthermia of super paramagnetic iron oxide nanoparticles (SPIONs). J Phys Chem C Nanomater Interfaces 114:19194–19201

    CAS  Article  Google Scholar 

  78. 78.

    Zhou H, Lee J, Park TJ et al (2012) Ultrasensitive DNA monitoring by au-Fe 3O 4 nanocomplex. Sensors Actuators B Chem 163:224–232

    CAS  Article  Google Scholar 

  79. 79.

    Wang L, Luo J, Fan Q et al (2005) Monodispersed core-shell Fe3O4@Au nanoparticles. J Phys Chem B 109:21593–21601

    CAS  Article  Google Scholar 

  80. 80.

    Robinson I, Tung LD, Maenosono S et al (2010) Synthesis of core-shell gold coated magnetic nanoparticles and their interaction with thiolated DNA. Nanoscale 2:2624

    CAS  Article  Google Scholar 

  81. 81.

    Dahal N, Chikan V, Jasinski J, Leppert V (2008) Synthesis of water-soluble iron− gold alloy nanoparticles. Chem Mater 17:6389–6395

    Article  CAS  Google Scholar 

  82. 82.

    Wei Y, Han B, Hu X et al (2012) Synthesis of Fe3O4 nanoparticles and their magnetic properties. Procedia Eng 27:632–637

    CAS  Article  Google Scholar 

  83. 83.

    Rawal R, Chawla S, Pundir CS (2012) An electrochemical sulfite biosensor based on gold coated magnetic nanoparticles modified gold electrode. Biosens Bioelectron 31:144–150

    CAS  Article  Google Scholar 

  84. 84.

    Nadagouda MN, Varma RS (2007) A greener synthesis of Core (Fe, cu)-shell (au, Pt, Pd, and Ag) nanocrystals using aqueous vitamin C. Cryst Growth Des 7:2582–2587

    CAS  Article  Google Scholar 

  85. 85.

    Ahmad T, Wani IA, Ahmed J, Al-Hartomy OA (2014) Effect of gold ion concentration on size and properties of gold nanoparticles in TritonX-100 based inverse microemulsions. Appl Nanosci 4:491–498

    CAS  Article  Google Scholar 

  86. 86.

    Sau TK, Murphy CJ (2004) Room temperature, high-yield synthesis of multiple shapes of gold nanoparticles in aqueous solution. J Am Chem Soc 126:8648–8649

    CAS  Article  Google Scholar 

  87. 87.

    Nowack B, Krug HF, Height M (2011) 120 years of nanosilver history: implications for policy makers. Environ Sci Technol 45:1177–1183

    CAS  Article  Google Scholar 

  88. 88.

    Enustun BV, Turkevich J (1963) Coagulation of colloidal gold. J Am Chem Soc 85:3317–3328

    CAS  Article  Google Scholar 

  89. 89.

    Xu Z, Hou Y, Sun S (2007) Magnetic core/shell Fe3O4/Au and Fe3O4/Au/Ag nanoparticles with tunable plasmonic properties. J Am Chem Soc 129:8698–8699

    CAS  Article  Google Scholar 

  90. 90.

    Brown KR, Walter DG, Natan MJ (2000) Seeding of colloidal Au nanoparticle solutions. 2. Improved control of particle size and shape. Chem Mater 12:306–313

    CAS  Article  Google Scholar 

  91. 91.

    Goon IY, Lai LMH, Lim M et al (2009) Fabrication and dispersion of gold-shell-protected magnetite nanoparticles: systematic control using polyethyleneimine. Chem Mater 21:673–681

    CAS  Article  Google Scholar 

  92. 92.

    Levin CS, Hofmann C, Ali TA et al (2009) Magnetic−plasmonic core−shell nanoparticles. ACS Nano 3:1379–1388

    CAS  Article  Google Scholar 

  93. 93.

    Lyon JL, Fleming DA, Stone MB et al (2004) Synthesis of Fe oxide core/Au shell nanoparticles by iterative hydroxylamine seeding. Nano Lett 4:719–723

    CAS  Article  Google Scholar 

  94. 94.

    Ma LL, Borwankar AU, Willsey BW et al (2013) Growth of textured thin Au coatings on iron oxide nanoparticles with near infrared absorbance. Nanotechnology 24:025606

    CAS  Article  Google Scholar 

  95. 95.

    Pal S, Morales M, Mukherjee P, Srikanth H (2009) Synthesis and magnetic properties of gold coated iron oxide nanoparticles. J Appl Phys 105:1–4

    Article  CAS  Google Scholar 

  96. 96.

    Wagstaff AJ, Brown SD, Holden MR et al (2012) Cisplatin drug delivery using gold-coated iron oxide nanoparticles for enhanced tumour targeting with external magnetic fields. Inorganica Chim Acta 393:328–333

    CAS  Article  Google Scholar 

  97. 97.

    Wang H, Brandl DW, Le F et al (2006) Nanorice: a hybrid plasmonic nanostructure. Nano Lett 6:827–832

    CAS  Article  Google Scholar 

  98. 98.

    Phan CM, Nguyen HM (2017) Role of capping agent in wet synthesis of nanoparticles. J Phys Chem A 121:3213–3219

    CAS  Article  Google Scholar 

  99. 99.

    Diggins FWE (1999) The true history of the discovery of penicillin, with refutation of the misinformation in the literature. Br J Biomed Sci 56:83–93

    CAS  Google Scholar 

  100. 100.

    Bao G, Mitragotri S, Tong S (2013) Multifunctional nanoparticles for drug delivery and molecular imaging. Annu Rev Biomed Eng 15:253–282

    CAS  Article  Google Scholar 

  101. 101.

    Rai M, Deshmukh SD, Ingle AP et al (2014) Metal nanoparticles: the protective nanoshield against virus infection. Crit Rev Microbiol 42:1–11

    Google Scholar 

  102. 102.

    Sreekumar TV, Das A, Chandra L et al (2009) Inherently colored antimicrobial fibers employing silver nanoparticles. J Biomed Nanotechnol 5:115–120

    CAS  Article  Google Scholar 

  103. 103.

    White CA, Toothaker RD, Smith AL, Slattery JT (1989) In vitro evaluation of the determinants of bactericidal activity of ampicillin dosing regimens against Escherichia coli. Antimicrob Agents Chemother 33:1046–1051

    CAS  Article  Google Scholar 

  104. 104.

    Panáček A, Kvítek L, Smékalová M et al (2018) Bacterial resistance to silver nanoparticles and how to overcome it. Nat Nanotechnol 13:65–71

    Article  CAS  Google Scholar 

  105. 105.

    Holtz RD, Souza Filho a G, Brocchi M et al (2010) Development of nanostructured silver vanadates decorated with silver nanoparticles as a novel antibacterial agent. Nanotechnology 21:185102

    CAS  Article  Google Scholar 

  106. 106.

    Verma VC, Kharwar RN, Gange AC (2010) Biosynthesis of antimicrobial silver nanoparticles by the endophytic fungus Aspergillus clavatus. Nanomedicine 5:33–40

    CAS  Article  Google Scholar 

  107. 107.

    Selvaraj V, Nirmala Grace A, Alagar M, Hamerton I (2010) Antimicrobial and anticancer efficacy of antineoplastic agent capped gold nanoparticles. J Biomed Nanotechnol 6:129–137

    CAS  Article  Google Scholar 

  108. 108.

    Mohamed MM, Fouad SA, Elshoky HA et al (2017) Antibacterial effect of gold nanoparticles against Corynebacterium pseudotuberculosis. Int J Vet Sci Med 5:23–29

    Article  Google Scholar 

  109. 109.

    Shamaila S, Zafar N, Riaz S et al (2016) Gold nanoparticles: an efficient antimicrobial agent against enteric bacterial human pathogen. Nanomaterials 6:71

    Article  CAS  Google Scholar 

  110. 110.

    Salmon SA, Watts JL (2000) Minimum inhibitory concentration determinations for various antimicrobial agents against 1570 bacterial isolates from turkey poults. Avian Dis 44:85

    CAS  Article  Google Scholar 

  111. 111.

    Erdogan A, Rao SSC (2015) Small intestinal fungal overgrowth. Curr Gastroenterol Rep 17:1–7

    Article  Google Scholar 

  112. 112.

    Zietse R, Zoutendijk R, Hoorn EJ (2009) Fluid, electrolyte and acid-base disorders associated with antibiotic therapy. Nat Rev Nephrol 5:193–202

    CAS  Article  Google Scholar 

  113. 113.

    Lu L, Sun RW-Y, Chen R et al (2008) Silver nanoparticles inhibit hepatitis B virus replication. Antivir Ther 13:253–262

    CAS  Google Scholar 

  114. 114.

    Rogers JV, Parkinson CV, Choi YW et al (2008) A preliminary assessment of silver nanoparticle inhibition of monkeypox virus plaque formation. Nanoscale Res Lett 3:129–133

    Article  CAS  Google Scholar 

  115. 115.

    Lara HH, Ixtepan-Turrent L, Garza-Treviño EN, Rodriguez-Padilla C (2010) PVP-coated silver nanoparticles block the transmission of cell-free and cell-associated HIV-1 in human cervical culture. J Nanobiotechnology 8:15

    Article  CAS  Google Scholar 

  116. 116.

    Lara HH, Ayala-Nuñez NV, Ixtepan-Turrent L, Rodriguez-Padilla C (2010) Mode of antiviral action of silver nanoparticles against HIV-1. J Nanobiotechnology 8:1

    Article  CAS  Google Scholar 

  117. 117.

    Baram-Pinto D, Shukla S, Gedanken A, Sarid R (2010) Inhibition of HSV-1 attachment, entry, and cell-to-cell spread by functionalized multivalent gold nanoparticles. Small 6:1044–1050

    CAS  Article  Google Scholar 

  118. 118.

    Di Gianvincenzo P, Marradi M, Martínez-Ávila OM et al (2010) Gold nanoparticles capped with sulfate-ended ligands as anti-HIV agents. Bioorg Med Chem Lett 20:2718–2721

    Article  CAS  Google Scholar 

  119. 119.

    Shionoiri N, Sato T, Fujimori Y et al (2012) Investigation of the antiviral properties of copper iodide nanoparticles against feline calicivirus. J Biosci Bioeng 113:580–586

    CAS  Article  Google Scholar 

  120. 120.

    Fujimori Y, Sato T, Hayata T et al (2012) Novel antiviral characteristics of nanosized copper(I) iodide particles showing inactivation activity against 2009 pandemic H1N1 influenza virus. Appl Environ Microbiol 78:951–955

    CAS  Article  Google Scholar 

  121. 121.

    World Health Organization (2017) Global hepatitis report, 2017

    Google Scholar 

  122. 122.

    World Health Organization (WHO) (2016) Progress report 2016, prevent HIV, test and treat all

    Google Scholar 

  123. 123.

    Halliwell B, Gutteridge JMC (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219:1–14

    CAS  Article  Google Scholar 

  124. 124.

    Radiologists RC of, Padhani A, Allen C, Carey B (2014) Recommendations for cross-sectional imaging in cancer management: computed tomography – CT magnetic resonance imaging – MRI positron emission tomography – PET-CT

    Google Scholar 

  125. 125.

    McRobbie DW, Moore EA, Graves MJ, Prince MR (2006) MRI from picture to proton. Cambridge University Press, Cambridge

    Book  Google Scholar 

  126. 126.

    Murphy KJ, Brunberg JA, Cohan RH (1996) Adverse reactions to gadolinium contrast media: a review of 36 cases. Am J Roentgenol 167:847–849

    CAS  Article  Google Scholar 

  127. 127.

    Rhee CM, Bahn I, Alexander EK, Brunelli SM (2012) Association between iodinated contrast media exposure and incident hyperthyroidism and hypothyroidism. Arch Intern Med 172:153

    CAS  Article  Google Scholar 

  128. 128.

    Lee M, Lee G, Park S-S et al (2005) Synthesis of TiO 2 / SiO 2 nanoparticles in a water-in-carbon-dioxide microemulsion and their photocatalytic activity, vol 31, pp 379–389

    Google Scholar 

  129. 129.

    Blasiak B, Van Veggel FCJM, Tomanek B (2013) Applications of nanoparticles for MRI cancer diagnosis and therapy. J Nanomater 2013:13-15

  130. 130.

    Li W, Chen X (2015) Gold nanoparticles for photoacoustic imaging. Nanomedicine 10:299–320

    CAS  Article  Google Scholar 

  131. 131.

    Stacul F, van der Molen AJ, Reimer P et al (2011) Contrast induced nephropathy: updated ESUR contrast media safety committee guidelines. Eur Radiol 21:2527–2541

    Article  Google Scholar 

  132. 132.

    van Schooneveld MM, Cormode DP, Koole R et al (2010) A fluorescent, paramagnetic and PEGylated gold/silica nanoparticle for MRI, CT and fluorescence imaging. Contrast Media Mol Imaging 5:231–236

    Article  CAS  Google Scholar 

  133. 133.

    Cheheltani R, Ezzibdeh RM, Chhour P et al (2016) Tunable, biodegradable gold nanoparticles as contrast agents for computed tomography and photoacoustic imaging. Biomaterials 102:87–97

    CAS  Article  Google Scholar 

  134. 134.

    Kojima C, Umeda Y, Ogawa M et al (2010) X-ray computed tomography contrast agents prepared by seeded growth of gold nanoparticles in PEGylated dendrimer. Nanotechnology 21:245104

    Article  CAS  Google Scholar 

  135. 135.

    Umeda Y, Kojima C, Harada A et al (2010) PEG-attached PAMAM dendrimers encapsulating gold nanoparticles: growing gold nanoparticles in the dendrimers for improvement of their photothermal properties. Bioconjug Chem 21:1559–1564

    CAS  Article  Google Scholar 

  136. 136.

    Li X, Wang C, Tan H et al (2016) Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques. Biomaterials 108:71–80

    Article  CAS  Google Scholar 

  137. 137.

    Wang Y, Xie X, Wang X et al (2004) Photoacoustic tomography of a nanoshell contrast agent in the in vivo rat brain. Nano Lett 4:1689–1692

    CAS  Article  Google Scholar 

  138. 138.

    Song J, Kim J, Hwang S et al (2016) “Smart” gold nanoparticles for photoacoustic imaging: an imaging contrast agent responsive to the cancer microenvironment and signal amplification via pH-induced aggregation. Chem Commun 52:8287–8290

    CAS  Article  Google Scholar 

  139. 139.

    Ashton JR, Castle KD, Qi Y et al (2018) Dual-energy CT imaging of tumor liposome delivery after gold nanoparticle-augmented radiation therapy. Theranostics 8:1782–1797

    CAS  Article  Google Scholar 

  140. 140.

    Xu M, Wang LV (2006) Photoacoustic imaging in biomedicine. Rev Sci Instrum 77:2115-2120

    Article  CAS  Google Scholar 

  141. 141.

    Huang X, El-Sayed IH, Qian W, El-Sayed MA (2006) Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 128:2115–2120

    CAS  Article  Google Scholar 

  142. 142.

    Hirsch LR, Stafford RJ, Bankson JA et al (2003) Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc Natl Acad Sci 100:13549–13554

    CAS  Article  Google Scholar 

  143. 143.

    Woodford O, Harriman A, McFarlane W, Wills C (2017) Dramatic effect of solvent on the rate of photobleaching of organic pyrrole-BF 2 (BOPHY) dyes. ChemPhotoChem 1:317–325

    CAS  Article  Google Scholar 

  144. 144.

    Ashton JR, Gottlin EB, Patz EF et al (2018) A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer. PLoS One 13:1–20

    Article  CAS  Google Scholar 

  145. 145.

    Buzea C, Pacheco II, Robbie K (2007) Nanomaterials and nanoparticles: sources and toxicity. Biointerphases 2:MR17–MR71

    Article  Google Scholar 

  146. 146.

    Moyano DF, Goldsmith M, Solfiell DJ et al (2012) Nanoparticle hydrophobicity dictates immune response. J Am Chem Soc 134:3965–3967

    CAS  Article  Google Scholar 

  147. 147.

    Boraschi D, Duschl A (2013) Nanoparticles and the immune system: safety and effects. Nanoparticles Immune Syst Saf Eff 11:2621–2624

    Google Scholar 

  148. 148.

    Lammers T, Kiessling F, Hennink WE, Storm G (2012) Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J Control Release 161:175–187

    CAS  Article  Google Scholar 

  149. 149.

    Bhumkar DR, Joshi HM, Sastry M, Pokharkar VB (2007) Chitosan reduced gold nanoparticles as novel carriers for transmucosal delivery of insulin. Pharm Res 24:1415–1426

    CAS  Article  Google Scholar 

  150. 150.

    Nam J, La WG, Hwang S et al (2013) PH-responsive assembly of gold nanoparticles and “spatiotemporally concerted” drug release for synergistic cancer therapy. ACS Nano 7:3388–3402

    CAS  Article  Google Scholar 

  151. 151.

    Sandström P, Boncheva M, Åkerman B (2003) Nonspecific and thiol-specific binding of DNA to gold nanoparticles. Langmuir 19:7537–7543

    Article  CAS  Google Scholar 

  152. 152.

    Rosi NL, Giljohann DA, Thaxton CS et al (2006) Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science 312:1027–1030

    CAS  Article  Google Scholar 

  153. 153.

    Ding Y, Jiang Z, Saha K et al (2014) Gold nanoparticles for nucleic acid delivery. Mol Ther 22:1075–1083

    CAS  Article  Google Scholar 

  154. 154.

    Giljohann DA, Seferos DS, Prigodich AE et al (2009) Gene regulation with polyvalent siRNA−nanoparticle conjugates. J Am Chem Soc 131:2072–2073

    CAS  Article  Google Scholar 

  155. 155.

    Yonezawa T, Onoue S, Kimizuka N (2002) Metal coating of DNA molecules by cationic, metastable gold nanoparticles. Chem Lett 31:1172–1173

    Article  Google Scholar 

  156. 156.

    Barron N, Piskareva O, Muniyappa M (2007) Targeted genetic modification of cell lines for recombinant protein production. Cytotechnology 53:65–73

    CAS  Article  Google Scholar 

  157. 157.

    Niidome T, Nakashima K, Takahashi H, Niidome Y (2004) Preparation of primary amine-modified gold nanoparticles and their transfection ability into cultivated cells. Electronic Supplementary Information (ESI) available: A TEM image of the complex at a w/w ratio of 11 Chem Commun 1978. See

  158. 158.

    Paciotti GF, Myer L, Weinreich D et al (2004) Colloidal gold: a novel nanoparticle vector for tumor directed drug delivery. Drug Deliv J Deliv Target Ther Agents 11:169–183

    CAS  Google Scholar 

  159. 159.

    Dixit V, Van Den Bossche J, Sherman DM et al (2006) Synthesis and grafting of thioctic acid-PEG-folate conjugates onto Au nanoparticles for selective targeting of folate receptor-positive tumor cells. Bioconjug Chem 17:603–609

    CAS  Article  Google Scholar 

  160. 160.

    Du Y, Xia L, Jo A et al (2018) Synthesis and evaluation of doxorubicin-loaded gold nanoparticles for tumor-targeted drug delivery. Bioconjug Chem 29:420–430

    CAS  Article  Google Scholar 

  161. 161.

    Kalimuthu K, Lubin B-C, Bazylevich A et al (2018) Gold nanoparticles stabilize peptide-drug-conjugates for sustained targeted drug delivery to cancer cells. J Nanobiotechnology 16:34

    Article  CAS  Google Scholar 

  162. 162.

    Gao H (2016) Progress and perspectives on targeting nanoparticles for brain drug delivery. Acta Pharm Sin B 6:268–286

    Article  Google Scholar 

  163. 163.

    Rosenblum D, Joshi N, Tao W et al (2018) Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun 9:1-12

  164. 164.

    Friedman AD, Claypool SE, Liu R (2013) The smart targeting of nanoparticles. Curr Pharm Des 19:6315–6329

    CAS  Article  Google Scholar 

  165. 165.

    Fay F, Scott CJ (2011) Antibody-targeted nanoparticles for cancer therapy. Immunotherapy 3:381–394

    CAS  Article  Google Scholar 

  166. 166.

    Carter T, Mulholland P, Chester K (2016) Antibody-targeted nanoparticles for cancer treatment. Immunotherapy 8:941–958

    CAS  Article  Google Scholar 

  167. 167.

    Okur AC, Erkoc P, Kizilel S (2016) Targeting cancer cells via tumor-homing peptide CREKA functional PEG nanoparticles. Colloids Surf B Biointerfaces 147:191–200

    CAS  Article  Google Scholar 

  168. 168.

    King A, Ndifon C, Lui S et al (2016) Tumor-homing peptides as tools for targeted delivery of payloads to the placenta. Sci Adv 2:1–16

    Article  CAS  Google Scholar 

  169. 169.

    Pardridge WM (2007) Blood–brain barrier delivery. Drug Discov Today 12:54–61

    CAS  Article  Google Scholar 

  170. 170.

    Gwenin VV, Gwenin CD, Kalaji M (2011) Colloidal gold modified with a genetically engineered nitroreductase: toward a novel enzyme delivery system for cancer prodrug therapy. Langmuir 27:14300–14307

    CAS  Article  Google Scholar 

  171. 171.

    Obaidat I, Issa B, Haik Y (2015) Magnetic properties of magnetic nanoparticles for efficient hyperthermia. Nanomaterials 5:63–89

    Article  CAS  Google Scholar 

  172. 172.

    Bødker F, Mørup S, Linderoth S (1994) Surface effects in metallic iron nanoparticles. Phys Rev Lett 72:282–285

    Article  Google Scholar 

  173. 173.

    Mody VV, Cox A, Shah S et al (2014) Magnetic nanoparticle drug delivery systems for targeting tumor. Appl Nanosci 4:385–392

    CAS  Article  Google Scholar 

  174. 174.

    Donaldson JD, Beyersmann D (2005) Cobalt and cobalt compounds. In: Ullmann’s encyclopedia of industrial chemistry. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, pp 467–497

    Google Scholar 

  175. 175.

    Crossgrove J, Zheng W (2004) Manganese toxicity upon overexposure. NMR Biomed 17:544–553

    CAS  Article  Google Scholar 

  176. 176.

    Karlsson HL, Gustafsson J, Cronholm P, Möller L (2009) Size-dependent toxicity of metal oxide particles-a comparison between nano- and micrometer size. Toxicol Lett 188:112–118

    CAS  Article  Google Scholar 

  177. 177.

    Soto K, Garza KM, Murr LE (2007) Cytotoxic effects of aggregated nanomaterials. Acta Biomater 3:351–358

    CAS  Article  Google Scholar 

  178. 178.

    Brunner TJ, Wick P, Manser P et al (2006) In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. Environ Sci Technol 40:4374–4381

    CAS  Article  Google Scholar 

  179. 179.

    Chia SL, Leong DT (2016) Reducing ZnO nanoparticles toxicity through silica coating. Heliyon 2:1–18

    Article  Google Scholar 

  180. 180.

    Mine E, Yamada A, Kobayashi Y et al (2003) Direct coating of gold nanoparticles with silica by a seeded polymerization technique. J Colloid Interface Sci 264:385–390

    CAS  Article  Google Scholar 

  181. 181.

    Cerruti MG, Sauthier M, Leonard D et al (2006) Gold and silica-coated gold nanoparticles as thermographic labels for DNA detection. Anal Chem 78:3282–3288

    CAS  Article  Google Scholar 

  182. 182.

    Kobayashi Y, Nagasu R, Shibuya K et al (2014) Synthesis of a colloid solution of silica-coated gold nanoparticles for X-ray imaging applications. J Nanopart Res 16:1-13

  183. 183.

    Tural B, Özkan N, Volkan M (2009) Preparation and characterization of polymer coated superparamagnetic magnetite nanoparticle agglomerates. J Phys Chem Solids 70:860–866

    CAS  Article  Google Scholar 

  184. 184.

    Wang Y, Dave RN, Pfeffer R (2004) Polymer coating/encapsulation of nanoparticles using a supercritical anti-solvent process. J Supercrit Fluids 28:85–99

    CAS  Article  Google Scholar 

  185. 185.

    Chen D, Li J, Shi C et al (2007) Properties of core-shell Ni-Au nanoparticles synthesized through a redox-transmetalation method in reverse microemulsion. Chem Mater 19:3399–3405

    CAS  Article  Google Scholar 

  186. 186.

    Jana NR (2003) Silver coated gold nanoparticles as new surface enhanced Raman substrate at low analyte concentration. Analyst 128:954

    CAS  Article  Google Scholar 

  187. 187.

    Dierks S (2005) Gold “MSDS” electronic space products international, pp 1–6

    Google Scholar 

  188. 188.

    Alexander JW (2009) History of the medical use of silver. Surg Infect 10:289–292

    Article  Google Scholar 

  189. 189.

    Marx DE, Barillo DJ (2014) Silver in medicine: the basic science. Burns 40:S9–S18

    Article  Google Scholar 

  190. 190.

    Shubayev VI, Pisanic TR, Jin S (2009) Magnetic nanoparticles for theragnostics. Adv Drug Deliv Rev 61:467–477

    CAS  Article  Google Scholar 

  191. 191.

    Gwenin VV, Gwenin CD, Kalaji M (2009) Gold coated magnetic particles enabling nitroreductase delivery to cancer cells. European Union Patent PCT/EP2010/062871

  192. 192.

    McBain SC, Yiu HHP, Dobson J (2008) Magnetic nanoparticles for gene and drug delivery. Int J Nanomedicine 3:169–180

    CAS  Google Scholar 

  193. 193.

    Veiseh O, Gunn JW, Zhang M (2010) Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Deliv Rev 62:284–304

    CAS  Article  Google Scholar 

  194. 194.

    Kayal S, Ramanujan RV (2010) Anti-Cancer drug loaded iron–gold core–shell nanoparticles (Fe@Au) for magnetic drug targeting. J Nanosci Nanotechnol 10:5527–5539

    CAS  Article  Google Scholar 

  195. 195.

    Dobson J (2006) Magnetic nanoparticles for drug delivery. Drug Dev Res 67:55–60

    CAS  Article  Google Scholar 

  196. 196.

    Arruebo M, Fernández-Pacheco R, Ibarra MR, Santamaría J (2007) Magnetic nanoparticles for drug delivery. Nanotoday 2:22–32

    Article  Google Scholar 

  197. 197.

    Bhana S, Lin G, Wang L et al (2015) Near-infrared-absorbing gold nanopopcorns with iron oxide cluster core for magnetically amplified photothermal and photodynamic cancer therapy. ACS Appl Mater Interfaces 7:11637–11647

    CAS  Article  Google Scholar 

  198. 198.

    Abadeer NS, Murphy CJ (2016) Recent progress in cancer thermal therapy using gold nanoparticles. J Phys Chem C 120:4691–4716

    CAS  Article  Google Scholar 

  199. 199.

    Kirui DK, Rey DA, Batt CA (2010) Gold hybrid nanoparticles for targeted phototherapy and cancer imaging. Nanotechnology 21:1-10

    Article  CAS  Google Scholar 

  200. 200.

    Lal S, Clare SE, Halas NJ (2008) Photothermal therapy : impending clinical impact. Acc Chem Res 41:1842–1851

    CAS  Article  Google Scholar 

  201. 201.

    Sotiriou GA, Starsich F, Dasargyri A et al (2014) Photothermal killing of cancer cells by the controlled plasmonic coupling of silica-coated Au/Fe2O3 nanoaggregates. Adv Funct Mater 24:2818–2827

    CAS  Article  Google Scholar 

  202. 202.

    Cho S-J, Jarrett BR, Louie AY, Kauzlarich SM (2006) Gold-coated iron nanoparticles: a novel magnetic resonance agent for T 1 and T 2 weighted imaging. Nanotechnology 17:640–644

    CAS  Article  Google Scholar 

  203. 203.

    Cheng L, Yang K, Li Y et al (2012) Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy. Biomaterials 33:2215–2222

    CAS  Article  Google Scholar 

  204. 204.

    Rajkumar S, Prabaharan M (2019) Multi-functional core-shell Fe3O4@ Au nanoparticles for cancer diagnosis and therapy. Colloids Surf B Biointerfaces 174:252–259

    Article  CAS  Google Scholar 

  205. 205.

    Izadiyan Z, Shameli K, Miyake M et al (2019) Green fabrication of biologically active magnetic core-shell Fe3O4/Au nanoparticles and their potential anticancer effect. Mater Sci Eng C 96:51–57

    CAS  Article  Google Scholar 

  206. 206.

    Kang N, Xu D, Han Y et al (2019) Magnetic targeting core/shell Fe3O4/Au nanoparticles for magnetic resonance/photoacoustic dual-modal imaging. Mater Sci Eng C 98:545–549

    CAS  Article  Google Scholar 

  207. 207.

    Searle PF, Chen MJ, Hu L et al (2004) Nitroreductase: a prodrug-activating enzyme for cancer gene therapy. Clin Exp Pharmacol Physiol 31:811–816

    CAS  Article  Google Scholar 

  208. 208.

    Patel P, Young JG, Mautner V et al (2009) A phase I/II clinical trial in localized prostate cancer of an adenovirus expressing nitroreductase with CB1984. Mol Ther 17:1292–1299

    CAS  Article  Google Scholar 

  209. 209.

    Palmer DH, Mautner V, Mirza D et al (2004) Virus-directed enzyme prodrug therapy: intratumoral administration of a replication-deficient adenovirus encoding nitroreductase to patients with resectable liver cancer. J Clin Oncol 22:1546–1552

    CAS  Article  Google Scholar 

  210. 210.

    Bagshawe KD (2005) Antibody-directed enzyme prodrug therapy professor. In: Valentino S, Borchardt R, Hageman M et al (eds) Prodrugs: challenges and rewards. Springer, New York, pp 526–536

    Google Scholar 

  211. 211.

    Sharma SK, Chester KA, Bagshawe KD (2014) Antibody-directed enzyme prodrug therapy (ADEPT). Handb Ther Antibodies Second Ed 1(4):475–486

    CAS  Google Scholar 

  212. 212.

    Gwenin CD, Kalaji M, Williams PA, Jones RM (2007) The orientationally controlled assembly of genetically modified enzymes in an amperometric biosensor. Biosens Bioelectron 22:2869–2875

    CAS  Article  Google Scholar 

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The authors thank the School of Chemistry at Bangor University for their support throughout this project, as well as funding from Welsh Government, the Life Sciences Research Network Wales, Cancer Research Wales and the Knowledge Economy Skills Scholarship (KESS).

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SDA coordinated the content, compilation, and writing of all sections, VVG proofed the paper and guided the content, tables and text. CDG coordinated the editing of all sections and final editing of the paper. All authors read and approved the final manuscript.

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Correspondence to Christopher D. Gwenin.

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Anderson, S.D., Gwenin, V.V. & Gwenin, C.D. Magnetic Functionalized Nanoparticles for Biomedical, Drug Delivery and Imaging Applications. Nanoscale Res Lett 14, 188 (2019).

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  • Nanoparticle
  • Drug delivery
  • Nanoparticle synthesis
  • Nanomedicine