What is a Silver Nanoparticle? And How Might It Improve My Health?

We answer your question of: “What is a Silver Nanoparticle? here. And, we go on to answer the follow-up question of: “How may it possibly improve my health?“, because let’s face it. Unless silver, or any other nanoparticle, has a beneficial function to perform most of us aren’t really going to be much interested.

Silver Nanoparticles Are Incredibly Small Particles

To the non-technically minded nano refers to incredibly small particles, far too small ever to see by eye in a normal microscope. So small in fact that they interact at the scale of chemical molecules. Silver nanoparticles are nanoparticles of silver of between 1 nm and 100 nm in size. While frequently described as being ‘silver’ some are composed of a large percentage of silver oxide due to their large ratio of surface to bulk silver atoms. Numerous shapes of nanoparticles can be constructed depending on the application at hand. Commonly used silver nanoparticles are spherical, but diamond, octagonal, and thin sheets are also common. It is this ability to design molecules to perform functions which will then kill bacteria and certain virus particles and also act in our favour during chemotherapy which makes silver nanoparticles so amazing.

Silver Nanoparticles Have An Extremely Large Surface Area

Their extremely large surface area permits the coordination of a vast number of ligands. The properties of silver nanoparticles applicable to human treatments are under investigation in laboratory and animal studies, assessing potential efficacy, toxicity, and costs.

As the particles grow, other molecules in the solution diffuse and attach to the surface. This process stabilizes the surface energy of the particle and blocks new silver ions from reaching the surface. The attachment of these capping/stabilizing agents slows and eventually stops the growth of the particle. The most common capping ligands are trisodium citrate and polyvinylpyrrolidone (PVP), but many others are also used in varying conditions to synthesize particles with particular sizes, shapes, and surface properties.

Size Distribution and Geometric Arrangements of the Nanoparticles

There are many different wet synthesis methods, including the use of reducing sugars, citrate reduction, reduction via sodium borohydride, the silver mirror reaction, the polyol process, seed-mediated growth, and light-mediated growth. Each of these methods, or a combination of methods, will offer differing degrees of control over the size distribution as well as distributions of geometric arrangements of the nanoparticle.

Silver Particles Are Separated and Collected

Once the particles have been formed in solution they must be separated and collected. There are several general methods to remove nanoparticles from solution, including evaporating the solvent phase or the addition of chemicals to the solution that lower the solubility of the nanoparticles in the solution. Both methods force the precipitation of the nanoparticles.

The size and shape of the nanoparticles produced are difficult to control and often have wide distributions. However, this method is often used to apply thin coatings of silver particles onto surfaces and further study into producing more uniformly sized nanoparticles is being done.

Silver Nanotechnology in Medicine and Therapeutic Drug Design

The introduction of nanotechnology into medicine is expected to advance diagnostic cancer imaging and the standards for therapeutic drug design. Nanotechnology may uncover insight about the structure, function and organizational level of the biosystem at the nanoscale.

Chemotherapeutic Applications Including Anti-cancer Drugs

Silver nanoparticles can undergo coating techniques that offer a uniform functionalized surface to which substrates can be added. When the nanoparticle is coated, for example, in silica the surface exists as silicic acid. Substrates can thus be added through the stable ether and ester linkages that are not degraded immediately by natural metabolic enzymes. Recent chemotherapeutic applications have designed anti-cancer drugs with a photocleavable linker, such as an ortho-nitrobenzyl bridge, attaching it to the substrate on the nanoparticle surface. The low toxicity nanoparticle complex can remain viable under metabolic attack for the time necessary to be distributed throughout the bodies systems.

Cancerous Tumour Treatment

If a cancerous tumour is being targeted for treatment, ultraviolet light can be introduced over the tumour region. The electromagnetic energy of the light causes the photoresponsive linker to break between the drug and the nanoparticle substrate. The drug is now cleaved and released in an unaltered active form to act on the cancerous tumour cells. Advantages anticipated for this method is that the drug is transported without highly toxic compounds, the drug is released without harmful radiation or relying on a specific chemical reaction to occur and the drug can be selectively released at a target tissue.

A second approach is to attach a chemotherapeutic drug directly to the functionalized surface of the silver nanoparticle combined with a nucleophilic species to undergo a displacement reaction. For example, once the nanoparticle drug complex enters or is in the vicinity of the target tissue or cells, a glutathione monoester can be administered to the site. The nucleophilic ester oxygen will attach to the functionalized surface of the nanoparticle through a new ester linkage while the drug is released to its surroundings. The drug is now active and can exert its biological function on the cells immediate to its surroundings limiting non-desirable interactions with other tissues – so that’s what a silver nanoparticle is all about for cancer patients.

Overcoming Multiple Drug Resistance During Chemotherapy Treatments

A major cause for the ineffectiveness of current chemotherapy treatments is multiple drug resistance (MDR) which can arise from several mechanisms.

Nanoparticles can provide a means to overcome MDR. In general, when using a targeting agent to deliver nanocarriers to cancer cells, it is imperative that the agent binds with high selectivity to molecules that are uniquely expressed on the cell surface. Hence NPs can be designed with proteins that specifically detect drug-resistant cells with overexpressed transporter proteins on their surface.

A pitfall of the commonly used nano-drug delivery systems is that free drugs that are released from the nanocarriers into the cytosol get exposed to the MDR transporters once again, and are exported. To solve this, 8 nm nanocrystalline silver particles were modified by the addition of trans-activating transcriptional activator (TAT), derived from the HIV-1 virus, which acts as a cell-penetrating peptide (CPP). Generally, AgNP effectiveness is limited due to the lack of efficient cellular uptake; however, CPP-modification has become one of the most efficient methods for improving the intracellular delivery of nanoparticles. Once ingested, the export of the AgNP is prevented based on size exclusion.

The concept is simple: the nanoparticles are too large to be effluxed by the MDR transporters because the efflux function is strictly subjected to the size of its substrates, which is generally limited to a range of 300-2000 Da. Thereby the nano particulates remain insusceptible to the efflux, providing a means to accumulate in high concentrations.

Introduction of Silver into Bacterial Cells to Induce Changes Leading to Cell Death and Sterilization

Introduction of silver into bacterial cells induces a high degree of structural and morphological changes, which can lead to cell death. As the silver nanoparticles come in contact with the bacteria, they adhere to the cell wall and cell membrane. Once bound, some of the silver passes through to the inside, and interacts with phosphate-containing compounds like DNA and RNA, while another portion adheres to the sulfur-containing proteins on the membrane. The silver-sulfur interactions at the membrane cause the cell wall to undergo structural changes, like the formation of pits and pores. Through these pores, cellular components are released into the extracellular fluid, simply due to the osmotic difference. Within the cell, the integration of silver creates a low molecular weight region where the DNA then condenses. Having DNA in a condensed state inhibits the cell’s replication proteins contact with the DNA. Thus the introduction of silver nanoparticles inhibits replication and is sufficient to cause the death of the cell. Further increasing their effect, when silver comes in contact with fluids, it tends to ionize which increases the nanoparticles’ bactericidal activity. This has been correlated to the suppression of enzymes and inhibited expression of proteins that relate to the cell’s ability to produce ATP.

Although it varies for every type of cell proposed, as their cell membrane composition varies greatly, It has been seen that in general, silver nanoparticles with an average size of 10 nm or less show electronic effects that greatly increase their bactericidal activity. This could also be partly due to the fact that as particle size decreases, reactivity increases due to the surface area to volume ratio increasing.

It has been noted that the introduction of silver nanoparticles has shown to have synergistic activity with common antibiotics already used today, such as; penicillin G, ampicillin, erythromycin, clindamycin, and vancomycin against E. coli and S. aureus. So, in answer to our question of “What is a Silver Nanoparticle” was can say that has a way of working with common antibiotics to potentially enhance them in some way.

Use of Silver Nanoparticles to Prevent Bacteria Growing on or Adhering to Surfaces

Silver nanoparticles can prevent bacteria from growing on or adhering to the surface. This can be especially useful in surgical settings where all surfaces in contact with the patient must be sterile. Silver nanoparticles can be incorporated on many types of surfaces including metals, plastic, and glass. In medical equipment, it has been shown that they lower the bacterial count on devices used compared to old techniques. However, the problem arises when the procedure is over and a new one must be done. In the process of washing the instruments a large portion of the silver nanoparticles become less effective due to the loss of silver ions. They are more commonly used in skin grafts for burn victims as the silver nanoparticles embedded with the graft provide better antimicrobial activity and result in significantly less scarring of the victim. These new applications are direct decedents of older practices that used silver nitrate to treat conditions such as skin ulcers. Now, silver nanoparticles are used in bandages and patches to help heal certain burns and wounds.

So what can silver nanoparticles do in such circumstances?  They “lower bacterial counts” – which to you and me means they kill bacteria!

Potable Water Treatment Method Potential

They also show promising application as a water treatment method to form clean potable water. This doesn’t sound like much, but water contains numerous diseases and some parts of the world do not have the luxury of clean water or any at all. It wasn’t new to use silver for removing microbes, but this experiment used the carbonate in the water to make microbes even more vulnerable to silver. First, the scientists of the experiment use the nanoparticles to remove certain pesticides from the water, ones that prove fatal to people if ingested. Several other tests have shown that the silver nanoparticles were capable of removing certain ions in water as well, like iron, lead, and arsenic. But that is not the only reason why the silver nanoparticles are so appealing, they do not require any external force (no electricity or hydraulics) for the reaction to occur. Conversely post-consumer silver nanoparticles in wastewater may adversely impact biological agents used in wastewater treatment.

Use of Silver Nanoparticles and Colloidal Silver in Consumer Goods

There are instances in which silver nanoparticles and colloidal silver are used in consumer goods. Samsung, for example, claimed that the use of silver nanoparticles in washing machines would help to sterilize clothes and water during the washing and rinsing functions and allow clothes to be cleaned without the need for hot water. The nanoparticles in these appliances are synthesized using electrolysis. Through electrolysis, silver is extracted from metal plates and then turned into silver nanoparticles by a reduction agent. This method avoids the drying, cleaning, and re-dispersion processes, which are generally required with alternative colloidal synthesis methods. Importantly, the electrolysis strategy also decreases the production cost of Ag nanoparticles, making these washing machines more affordable to manufacture. Samsung has described a system as follows:

A grapefruit-sized device alongside the washer tub uses electrical currents to nanoshave two silver plates the size of large chewing gum sticks. Resulting in positively charged silver atoms-silver ions (Ag+)-are injected into the tub during the wash cycle.

Samsung’s description of the Ag nanoparticle generating process seems to contradict its advertisement of silver nanoparticles. Instead, the statement indicates that laundry cycles. When clothes are run through the cycle, the intended mode of action is that bacteria contained in the water are sterilized as they interact with the silver present in the washing tub. As a result, these washing machines can provide antibacterial and sterilization benefits on top of conventional washing methods.

Samsung has commented on the lifetime of these silver-containing washing machines. The electrolysis of silver generates over 400 billion silver ions during each wash cycle. Given the size of the silver source (two “gum-sized” plate of Ag), Samsung estimates that these plates can last up to 3000 wash cycles.

These plans by Samsung were not overlooked by regulatory agencies. Agencies investigating nanoparticle use include but are not limited to: the U.S. FDA, U.S. EPA, SIAA of Japan, and Korea’s Testing and Research Institute for Chemical Industry and FITI Testing & Research Institute. These various agencies plan to regulate silver nanoparticles in appliances.

These washing machines are some of the first cases in which the EPA has sought to regulate nanoparticles in consumer goods. Samsung stated that the silver gets washed away in the sewer and regulatory agencies worry over what that means for wastewater treatment streams. Currently, the EPA classifies silver nanoparticles as pesticides due to their use as antimicrobial agents in wastewater purification. The washing machines being developed by Samsung do contain a pesticide and have to be registered and tested for safety under the law, particularly the US Federal insecticide, fungicide and rodenticide act. The difficulty, however behind regulating nanotechnology in this manner is that there is no distinct way to measure toxicity.

Silver Nanoparticles Used in Colourants in Cosmetics

In addition to the uses described above, the European Union Observatory for Nanomaterials (EUON) has highlighted that silver nanoparticles are used in colourants in cosmetics, as well as pigments. A recently published study by the EUON has illustrated the existence of knowledge gaps regarding the safety of nanoparticles in pigments.

What are the Silver Nanoparticle Effects on Human Health?

Although silver nanoparticles are widely used in a variety of commercial products, there has only recently been a major effort to study their effects on human health. There have been several studies that describe the in vitro toxicity of silver nanoparticles to a variety of different organs, including the lung, liver, skin, brain, and reproductive organs. The mechanism of the toxicity of silver nanoparticles to human cells appears to be derived from oxidative stress and inflammation that is caused by the generation of reactive oxygen species (ROS) stimulated by either the Ag NPs, Ag ions, or both. For example, Park et al. showed that exposure of a mouse peritoneal macrophage cell line (RAW267.7) to silver nanoparticles decreased the cell viability in a concentration- and time-dependent manner. They further showed that the intracellular reduced glutathionine (GSH), which is a ROS scavenger, decreased to 81.4% of the control group of silver nanoparticles at 1.6 ppm.

What are the Silver Nanoparticle General Toxic Effects?

Since silver nanoparticles undergo dissolution releasing silver ions, which is well-documented to have toxic effects, there have been several studies that have been conducted to determine whether the toxicity of silver nanoparticles is derived from the release of silver ions or from the nanoparticle itself. Several studies suggest that the toxicity of silver nanoparticles is attributed to their release of silver ions in cells as both silver nanoparticles and silver ions have been reported to have similar cytotoxicity. For example, In some cases, it is reported that silver nanoparticles facilitate the release of toxic free silver ions in cells via a “Trojan-horse type mechanism,” where the particle enters cells and is then ionized within the cell.

However, there have been reports that suggest that a combination of silver nanoparticles and ions is responsible for the toxic effect of silver nanoparticles. Navarro et al. using cysteine ligands as a tool to measure the concentration of free silver in solution, determined that although initially, silver ions were 18 times more likely to inhibit the photosynthesis of algae, Chlamydomanas reinhardtii, but after 2 hours of incubation it was revealed that the algae containing silver nanoparticles were more toxic than just silver ions alone. Furthermore, there are studies that suggest that silver nanoparticles induce toxicity independent of free silver ions. For example, Asharani et al. compared phenotypic defects observed in zebrafish treated with silver nanoparticles and silver ions and determined that the phenotypic defects observed with silver nanoparticle treatment were not observed with silver ion-treated embryos, suggesting that the toxicity of silver nanoparticles is independent of silver ions.

Protein channels and nuclear membrane pores can often be in the size range of 9 nm to 10 nm in diameter. Small silver nanoparticles constructed of this size have the ability to not only pass through the membrane to interact with internal structures but also to be become lodged within the membrane. Silver nanoparticle depositions in the membrane can impact the regulation of solutes, exchange of proteins and cell recognition. Exposure to silver nanoparticles has been associated with “inflammatory, oxidative, genotoxic, and cytotoxic consequences”; the silver particulates primarily accumulate in the liver. but have also been shown to be toxic in other organs including the brain. Nano-silver applied to tissue-cultured human cells leads to the formation of free radicals, raising concerns about potential health risks.

Featured Image Background Attribution: Theivasanthi / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0)

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