Investigating the versatility of multifunctional silver nanoparticles: preparation and inspection of their potential as wound treatment agents

Abstract

The use of silver as a medicinal substance dates back to the times of Hippocrates, the father of modern medicine who used silver’s medical properties to treat wounds [ 1 ]. Historically, silver was considered one of the most important antibacterial agents before the introduction of antibiotics [ 2 ]. Prior to the discovery of antibiotics, the desperate need of materials with antibacterial properties was followed by the application of silver in sutures, postoperative inflammation and infection prevention, and treatment of battle wounds during World War I. Usage of antibiotics, enzymes, metal ions, and quaternary ammonium compounds poses disadvantages, including the development of drug resistance and detrimental effects regarding the environment [ 3 ]. Numerous theories of the antibacterial mechanism of silver have been suggested in the past as the interest in silver’s ability to fight microorganisms grew. Silver atoms are known to attach to the sulfur in thiol of vital enzymes involved in biological processes including ion transport and transmembrane energy generation [ 4 ]. Silver acts as a reducing agent to catalyze the reaction between cellular oxygen and hydrogen of thiol groups resulting in disulfide bonds [ 5 ]. Modifications in vital cellular molecules can provoke alterations in the cellular structure causing malfunctions that may finally result in apoptosis or necrosis. Disruption of cell respiration is a sure-fire cause of cell death. A decrease in the expression of maltose transporter, succinyl-coenzyme A synthetase, 30S ribosomal subunit protein, and fructose bisphosphate aldolase was observed in the cells treated with a 900 ppb silver ion solution [ 6 ]. The silver ions deactivate the 30S ribosomal subunit by binding to it. The deactivation of the ribosome complex leads to the interference in the translation of proteins [ 6 ]. Succinyl-coenzyme A synthase, a crucial component of the TCA cycle, catalyzes the reaction that yields succinate from succinyl-CoA and simultaneously phosphorylates ADP to make ATP [ 7 ]. Disruption of glycolysis via silver is caused by the deactivation of fructose bisphosphate aldolase. Fructose bisphosphate aldolase catalyzes the cleavage of fructose-1,6-bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate [ 7 ]. A maltose transporter, MalK, present in the cytoplasmic membrane is another vital organelle affected by the silver [ 8 ]. The disruption of any one of these processes can contribute to the mortality of bacterial cells. Other mechanisms regarding silver’s mechanism of action concerns silver’s intracellular interaction with differing cell components. Klueh et al. proposed that Ag + ions can enter cells and denature DNA molecules especially by disrupting the hydrogen bonds between purine and pyrimidine base pairs [ 4 ]. The presence of numerous possible disruptions of cell functions may explain silver’s capability of inhibiting bacterial growth of various species. Silver is currently used in wound dressings [ 9 ], endotracheal tubes [ 10 ], surgical masks [ 11 ], cotton fibers [ 12 ], drinking water purification [ 13 ], antibacterial glass [ 7 ], food packaging [ 14 ], clothing, burn wound-care cream, and many other everyday applications. The antibacterial properties of silver are only exhibited in its ionic form. It has been reported that non-ionized silver from an insoluble silver source is unable to inhibit the growth of bacteria [ 15 ]. Among silver salts, silver sulfadiazine (AgSD) is commonly used as a source of silver ions and is known as a broad-spectrum antimicrobial substance [ 16 ]. Using its wide range of effectiveness against bacteria, silver sulfadiazine has been widely used in burn wound-care. Topical cream containing the AgSD is currently commercially available. In many studies regarding the antibacterial properties of silver and silver nanoparticles, silver sulfadiazine is considered the gold standard and is used to compare the potency of the bactericidal activity of novel substances [ 17 ]. By first understanding the mechanism of action of the antibacterial activity of silver at a molecular level, the compound can be improved upon by not only decreasing its size, but also by carrying out modifications that result in synergism.