|Year : 2015 | Volume
| Issue : 1 | Page : 35-38
Silver nanoparticles: A boon in clinical medicine
Aashritha Shenava1, S Mahalinga Sharma2, Veena Shetty3, Shilpa Shenoy4
1 Department of Prosthodontics and Implantology, A B Shetty Institute of Dental Sciences, Mangalore, Karnataka, India
2 Department of Oral and Maxillofacial Surgery, A B Shetty Institute of Dental Sciences, Mangalore, Karnataka, India
3 Department of Microbiology, A B Shetty Institute of Dental Sciences, Mangalore, Karnataka, India
4 Department of Microbiology, K S Hegde Medical Academy, Mangalore, Karnataka, India
|Date of Web Publication||7-Jul-2015|
Department of Prosthodontics and Implantology, A B Shetty Institute of Dental Sciences, Mangalore - 575 018, Karnataka
Source of Support: None, Conflict of Interest: None
Silver nanoparticles (AgNP) have unique properties which help in molecular diagnostics, in therapies, as well as in devices that are used in several medical procedures. AgNP are nanoparticles of silver which are in the range of 1 and 100 nm in size. The major methods used for AgNP synthesis are the physical and chemical methods. The major applications of AgNP in the medical field include diagnostic applications and therapeutic applications. In most of the therapeutic applications, it is the antimicrobial property that is being majorly explored though the anti-viral property has its fair share of applications. This review provides a comprehensive view on the synthesis and applications of nanoparticles in the medical field. The focus is on exploring their various prospective applications besides trying to understand the current scenario.
Keywords: Medical applications silver nanoparticles, silver nanoparticles, synthesis
|How to cite this article:|
Shenava A, Sharma S M, Shetty V, Shenoy S. Silver nanoparticles: A boon in clinical medicine. J Oral Res Rev 2015;7:35-8
|How to cite this URL:|
Shenava A, Sharma S M, Shetty V, Shenoy S. Silver nanoparticles: A boon in clinical medicine. J Oral Res Rev [serial online] 2015 [cited 2021 Jun 24];7:35-8. Available from: https://www.jorr.org/text.asp?2015/7/1/35/160194
| Introduction|| |
For centuries, silver (Ag) compounds and ions have been extensively used for both hygienic and healing purposes, due to their strong bactericidal effects, as well as a broad spectrum antimicrobial activity. , Due to increased resistance of bacteria to antibiotics and improvements in polymer technology, it resulted in a large number of Ag-containing dressings being available on the market. Ag is applied to burns, either in the form of impregnated bandages or as a cream containing Ag sulfadiazine as the active agent, a product that is still considered the benchmark Ag product.  Ag-based dressings are now available as a variety of fibers or polymeric scaffolds impregnated or coated with an Ag salt or metallic Ag in nanoparticulate form. They all exhibit fast and broad-spectrum antibacterial activity against both Gram-positive and negative bacteria. , In recent years, the mechanism of action of Ag has been investigated: It seems that Ag shows a multilevel antibacterial effect, due to blockage of respiratory enzyme pathways, as well as alteration of microbial DNA and the cell wall.  Ag has been demonstrated to be effective also against multidrug-resistant organisms. 
| Methods of Literature Search|| |
In this regard, the reports of the following review include a literature search in PubMed.
Synthesis of silver nanoparticles
Citrate synthesis (the Turkevich method)
In 1951, Turkevich et al. described a synthesis of hydrophilic gold nanoparticles (NP) by the reduction of chloroauric acid with sodium citrate in an aqueous solution on boiling.  According to the data from transmission electron microscopy, the synthesized NP were spherical, had a narrow size distribution and the average diameter of 20 ± 1.5 nm. Later, the Turkevich method was used in the preparation of AgNP.  However, whereas Turkevich managed to obtain spherical gold NP with a narrow size distribution, for Ag, the diameter of synthesized different-shaped aggregates varied in the range of 60 ± 200 nm. Despite its considerable drawbacks, the citrate method was widely used for the synthesis of AgNP. A distinguishing feature of the Turkevich method is that citrate ions simultaneously act as a reducing agent and a stabilizer. This complicates the selection of their optimal concentration because its variations simultaneously affect the reduction rate and the nucleation and growth of particles. Moreover, the oxidation products of citrate anions (acetonedicarboxylic and itaconic acids) can adsorb on the NP surface thus affecting their further growth. Apparently, to elucidate the stabilizing role of citrate anions, one has to reduce a metal salt under conditions unfavorable for the reduction of metal ions with citrate (e.g., at room temperature). 
Biological properties of silver nanoparticles
Antimicrobial effects of silver nanoparticles against bacterial cells
Microbes are found everywhere and can be harmful if they find a way to invade the human body. They are becoming even more dangerous because the number of antibiotic resistant microbes is increasing. Araujo et al. in 2011 have quoted NP are used in dental materials to combat the spread of microbes and are used in the prevention of bacterial colonization on the surfaces of prostheses. These are surfaces that are commonly used by humans and could harbor bacteria. AgNP have antibacterial properties and are nontoxic to humans in low concentrations. Araujo et al. 2011 NP can inactive proteins, blocking respiration and electron transfer, and subsequent inactivating the bacteria. Inactivation of the bacteria does not allow them to reproduce and will result in a sanitized surface. The NP are able to interact with the microbes because the "cell wall peptidoglycans contain negatively charged molecules that will likely interact electrostatically with the Ag ions." The AgNP naturally have a positive charge, which causes them to be attracted to the negatively charged molecules within the cell wall and causes damage to the cell by interruption of its natural processes. The antibacterial properties of the AgNP depend on the size of the particles; the smaller the particles, the greater the effect. The particle size is a major factor because the smaller the particle, the greater the surface area, which allows for greater interaction with the bacteria. "NP and Ag ions interact with sulfur-containing compounds found in the bacterial membrane protein and with phosphorous-containing compounds, such as DNA." The interaction with the DNA can also cause a decrease in microbe reproduction, allowing the antimicrobial effects on surfaces to be successful. Inhibiting microbe reproduction with AgNP decreases the harm that microbes can cause to humans. This can lead to more sterilized environments that could otherwise be overlooked and result in harm. 
Current use of silver nanoparticles in medicine
Nanosilver in diagnosis and imaging
The plasmonic properties of nano-Ag strongly depend on its size, shape, and dielectric medium that surrounds it.  In fact, the latter dependency can be exploited in biosensing. Most biomolecules have a higher refractive index than buffer solutions so when attached on nano-Ag, the local refractive index increases shifting the Ag extinction (absorption and scattering) spectrum. Biosensors utilizing plasmonic nanostructures (local surface plasmon resonance-LSPR) are advantageous over commercial thin, plasmonic, continuous films (surface plasmon resonance-SPR).  Triangular nano-Ag particles made by lithography were deposited on substrates to monitor interactions between biomolecules, such as biotin-streptavidin and to monitor two biomolecules related to Alzheimer's disease. , Nano-Ag cubes or rhombi can also be employed in biosensing of protein interactions. Lately, nano-Ag plasmonic biosensors are promising for cancer detection. ,, Recently, the employment of silica-coated nano-Ag as biosensors for the detection of bovine serum albumin was demonstrated with excellent solution dispersion and limited antibacterial activity. Bioimaging plasmonic particles, such as nano-Ag, can be detected by numerous optical microscopy techniques and are advantageous over commonly used fluorescent organic dyes that decompose during imaging (photobleaching). In contrast, nano-Ag is photostable allowing thus its use as a biological probe to monitor continuously dynamic events for an extended period of time.  The plasmonic properties of such small metallic NP enable them also to be employed also as an in vivo therapeutic tool. Plasmonic particles are conjugated to biological targets such as cancer cells or tissues and are used to absorb light and convert it into thermal energy.  This destroys the targets by thermal ablation, enabling such particles to be used in a non-invasive cancer treatment. Typically, gold NP are used as they are relatively less toxic than nano-Ag. In fact, this potential toxicity of plasmonically superior nano-Ag is its main limitation since it may destroy the cell motivating the development of hermetically-coated nano-Ag.  There are two ways to employ nano-Ag for bioimaging: Either incubated with cells and monitor their physical interactions and uptake or to functionalize the nano-Ag surface with a biomolecule that binds specifically to sites on the cell membrane. The former is easier as the latter needs a specific biofunctionalization molecule. Nano-Ag particles incubated with neuroblastoma cells were detected nicely under dark-field illumination but exhibited toxicity. 
Nanosilver in therapeutics
Wound dressing: Antiseptic agents are now considered for the treatment of localized skin and wound infections because they have a lower propensity to induce bacterial resistance than antibiotics. One example of the early use of Ag in wound care is Ag sulfadiazine cream, developed in the 1960s, for the treatment of burns. Recently, a trend toward the use of wound cover dressings that contain Ag has been evident, and today, a selection of foam, film, hydrocolloid, gauze, and dressings with Hydro fiber technology impregnated with Ag are commercially available. ,
Future therapeutic directions of Silver nanoparticles
Magnetic field hyperthermia: Cancer treatment with AC magnetic field
There are many different treatments for cancer. Hyperthermia is one of the possible treatments being studied. Hyperthermia is the "heating of certain organ or tissues to a temperature between 41°C and 46°C" (Jordan et al., 1999). By heating tissue within that range, it causes damage to the cells because they cannot function at high temperatures. Their lack of function occurs because proteins begin to denature, and damage occurs in the cell but not enough to cause cell death. Unfortunately, with hyperthermia, it is difficult to target specific cells, for example, cancer cells, without using a targeting agent. To obtain a more concentrated dose of hyperthermia, magnetic particles are used with magnetic fields at specific sites. "Subdomain particles (nanometer in size) absorb much more power at tolerable AC magnetic fields than is obtained by well-known hysteresis heating of multidomain (microns in size) particles" (Jordan et al., 1998). These NP have a magnetic core that allows them to develop a magnetic moment. This is important because the magnetic moment of a particle at rest has no specific orientation. Once a magnetic field is applied, the particle lines up along the field lines. If the magnetic field is changed, the particle will rotate to realign with the new field lines. If the fields are constantly changing as they are with AC magnetic fields, then the particle will constantly be rotating from one orientation to another. This oscillation creates a transfer of energy that resembles friction which produces heat. This heat can build up resulting in hyperthermia in the tissue where the magnetic NP are present. This is a promising treatment for cancer because "a tumor, which has taken up these particles, will not be able to get rid of them" (Jordan et al., 1998). This means if the tumor cells grow between treatments, their daughter cells will have some of these NP inside of them. This implies that only one dose needs to be administered, and future applications of AC magnetic fields will affect the daughter cells. Magnetic field hyperthermia is a promising technology because with the magnetic NP, it is more specific to cancer cells and more damaging. 
A luciferase-based assay showed that AgNP coated with PVP were an effective virucidal agent against the cell-free virus (including laboratory strains, clinical isolates, T and M tropic strains, and resistant strains) and cell-associated virus. The concentration of AgNP at which infectivity was inhibited by 50% (IC50) ranged from 0.44 to 0.91 mg/mL. The observed antiviral effect of AgNP was due to the NP, rather than just to the Ag ions present in the solution. In fact, Ag salts exerting an antibacterial effect through Ag ions, inhibited HIV-1 with a therapeutic index 12 times lower than the one of AgNP. AgNP inhibit the initial stages of the HIV-1 infection cycle by blocking adsorption and infectivity in a cell fusion assay. The inhibitory activity of AgNP against the gp120-CD4 interaction was also investigated in a competitive gp120-capture ELISA, which together with the cell-based fusion assay, showed that AgNP inhibit HIV-1 infection by blocking viral entry, particularly the gp120-CD4 interaction. Besides, AgNP inhibit postentry stages of the HIV-1 life cycle, in fact, the antiviral activity was maintained also when the metal NP were added 12 h after the cell had been infected with HIV. Since Ag ions can form complexes with electron donor groups containing sulfur, oxygen, or nitrogen that are normally present as thiols or phosphates on amino acids and nucleic acids they might inhibit postentry stages of infection by blocking HIV-1 proteins other than gp120, or reducing reverse transcription or proviral transcription rates by directly binding to the RNA or DNA molecules. AgNP proved to be virucidal to cell-free and cell-associated HIV-1 as judged by viral infectivity assays. HIV infection was effectively eliminated following short exposure of isolated virus to AgNP. These properties make AgNP a potential broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains. 
As an anti-platelet agent
AgNP inhibited platelet functional responses like adhesion to immobilized fibrinogen F-actin reorganization and platelet cytoskeletal changes namely fibrin clot retraction in a dose-dependent manner, irrespective of the nature of agonists used. Thus, significant inhibition of platelet functions with a relatively low dose of nano-Ag, raise the hope for its use as an antiplatelet therapeutic agent. 
| Discussion|| |
The therapeutic use of AgNP is many; in dentistry, it has been advocated as an antifungal agent and has been used against candidiasis. In the cancer treatment, the magnetic field hyperthermia is a promising technology because with the magnetic NP it is more specific to cancer cells and more damaging.  AgNP proved to be virucidal to cell-free and cell-associated HIV-1 as judged by viral infectivity assays. HIV infection was effectively eliminated following short exposure of isolated virus to AgNP. These properties make AgNP a potential broad-spectrum agent not prone to inducing resistance that could be used preventively against a wide variety of circulating HIV-1 strains.  Other uses include burns dressing, as biosensors in diagnosis and imaging.
| Conclusion|| |
The advance in nanotechnology has enabled us to utilize particles in the size of the nanoscale. This has created new therapeutic horizons, and in the case of Ag, the current data reveal the surface of the potential benefits and the wide range of applications.
Financial support and sponsorship
Conflict of interest
There are no conflicts of interest.
| References|| |
Klasen HJ. Historical review of the use of silver in the treatment of burns. I. Early uses. Burns 2000;26:117-30.
Klasen HJ. A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver. Burns 2000;26:131-8.
Hussain S, Ferguson C. Best evidence topic report. Silver sulphadiazine cream in burns. Emerg Med J 2006;23:929-32.
Castellano JJ, Shafii SM, Ko F, Donate G, Wright TE, Mannari RJ, et al.
Comparative evaluation of silver-containing antimicrobial dressings and drugs. Int Wound J 2007;4:114-22.
Ip M, Lui SL, Poon VK, Lung I, Burd A. Antimicrobial activities of silver dressings: An in vitro
comparison. J Med Microbiol 2006;55:59-63.
Melayie A, Youngs JW. Silver and its application on antimicrobial agents. Expert Opin Ther Pat 2005;15:125-30.
Silvestry-Rodriguez N, Sicairos-Ruelas EE, Gerba CP, Bright KR. Silver as a disinfectant. Rev Environ Contam Toxicol 2007;191:23-45.
Turkevich J, Stevenson PC, Hiller J. Some effects on the flow of concentrated suspensions of variations in particle size and shape. Discuss Faraday Soc 1951;11:55.
Lee PC, Meisel D. Adsorption and surface-enhanced Raman of dyes on silver and gold sols. J Phys Chem 1982;86:3391-5.
Tripathi GN, Clements M. Adsorption of 2-mercaptopyrimidine on silver nanoparticles in water. J Phys Chem B 2003;107:11125-32.
Araújo EA, Andrade NJ, Da Silva LH, Bernardes PC, De C Teixeira AV, De Sá JP. J Food Prot 2012;75:701-5.
Kreibig U, Vollmer M. Optical Properties of Metal Clusters. Berlin, Germany: Springer; 1995.
Zhang JZ, Noguez C. Plasmonic optical properties and applications of metal nanostructures. Plasmonics 2008;3:127-50.
Haes AJ, Van Duyne RP. A nanoscale optical biosensor: Sensitivity and selectivity of an approach based on the localized surface plasmon resonance spectroscopy of triangular silver nanoparticles. J Am Chem Soc 2002;124:10596-604.
Haes AJ, Hall WP, Chang L, Klein WL, Van Duyne RP. A localized surface plasmon resonancebiosensor: First steps toward an assay for Alzheimer's disease. Nano Lett 2004;4:1029-34.
Galush WJ, Shelby SA, Mulvihill MJ, Tao A, Yang P, Groves JT. A nanocube plasmonic sensor for molecular binding on membrane surfaces. Nano Lett 2009;9:2077-82.
Zhu SL, Li F, Du CL, Fu YQ. A localized surface plasmon resonance nanosensor based onrhombic Ag nanoparticle array. Sens Actuators B Chem 2008;134:193-8.
Zhou W, Ma Y, Yang H, Ding Y, Luo X. A label-free biosensor based on silver nanoparticles array for clinical detection of serum p53 in head and neck squamous cell carcinoma. Int J Nanomedicine 2011;6:381-6.
Lee KJ, Nallathamby PD, Browning LM, Osgood CJ, Xu XH. In vivo
imaging of transport and biocompatibility of single silver nanoparticles in early development of zebrafish embryos. ACS Nano 2007;1:133-43.
Loo C, Lowery A, Halas N, West J, Drezek R. Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 2005;5:709-11.
Sotiriou GA, Hirt AM, Lozach PY, Teleki A, Krumeich F, Pratsinis SE. Hybrid, silica-coated, Janus-like plasmonic-magnetic nanoparticles. Chem Mater 2011;23:1985-992.
Schrand AM, Braydich-Stolle LK, Schlager JJ, Dai L, Hussain SM. Can silver nanoparticles be useful as potential biological labels? Nanotechnology 2008;19:235104.
Pirnay JP, De Vos D, Cochez C, Bilocq F, Pirson J, Struelens M, et al.
Molecular epidemiology of Pseudomonas aeruginosa
colonization in a burn unit: Persistence of a multidrug-resistant clone and a silver sulfadiazine-resistant clone. J Clin Microbiol 2003;41:1192-202.
Gupta A, Phung LT, Taylor DE, Silver S. Silver resistancein plasmids of the IncH incompatibility group and on Escherichia coli
chromosome. Microbiology 2001;147:3393-402.
Jordan A, Scholz R, Wust P, Fahline H, Roland F. (1999) Magnetic Fluid Hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superpara magnetic nanoparticles. J Magn Magn Mater 1999:413-9.
Galdiero S, Falanga A, Vitiello M, Cantisani M, Marra V, Galdiero M. Silver nanoparticles as potential antiviral agents. Molecules 2011;16:8894-918.
Bandyopadhyay D, Baruah H, Gupta B, Sharma S. Silver nano particles prevent platelet adhesion on immobilized fibrinogen. Indian J Clin Biochem 2012;27:164-70.
|This article has been cited by|
||The effects of silver nanoparticles exposure on the testicular antioxidant system during pre-pubertal rat stage
| ||Ingra Monique Duarte Lopes,Isabela Medeiros de Oliveira,Paula Bargi-Souza,Monica Degraf Cavallin,Christiane Schineider Machado Kolc,Najeh Maissar Khalil,Sueli Pércio Quináia,Marco Aurelio Romano,Renata Marino Romano |
| ||Chemical Research in Toxicology. 2019; |
|[Pubmed] | [DOI]|
||Silver nanoparticles in dentistry
| ||Victor T. Noronha,Amauri J. Paula,Gabriela Durán,Andre Galembeck,Karina Cogo-Müller,Michelle Franz-Montan,Nelson Durán |
| ||Dental Materials. 2017; |
|[Pubmed] | [DOI]|
||Toxic impact of nanomaterials on microbes, plants and animals
| ||Mohammed Nadim Sardoiwala,Babita Kaundal,Subhasree Roy Choudhury |
| ||Environmental Chemistry Letters. 2017; |
|[Pubmed] | [DOI]|
||Silver Nanoparticles (AgNP) in the Environment: a Review of Potential Risks on Human and Environmental Health
| ||Sein León-Silva,Fabián Fernández-Luqueño,Fernando López-Valdez |
| ||Water, Air, & Soil Pollution. 2016; 227(9) |
|[Pubmed] | [DOI]|
||Toxicological Considerations, Toxicity Assessment, and Risk Management of Inhaled Nanoparticles
| ||Shahnaz Bakand,Amanda Hayes |
| ||International Journal of Molecular Sciences. 2016; 17(6): 929 |
|[Pubmed] | [DOI]|