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Nanomaterials 2018, 8, 681 4 of 25 many sorption sites found on their extensive surface [69], AgNPs are also used in various analytical applications. There are manifold research studies which particularly describe the biocide activity of silver itself [70]. The current state of the art relies on the beneficial conjunction between antimicrobial silver nanoparticles and natural or synthetic polymers, in the modern attempt to diminish or even eliminate the microbial contamination and colonization processes [71]. The major advantage of nanosilver-based biomaterials designed for unconventional antibacterial applications is related to their intrinsic anti-pathogenic effects exhibited against both planktonic and biofilm-organized microorganisms. The bactericidal activity of AgNPs is attributed to silver cations, which possess the ability to specifically bind to thiol groups of bacterial proteins, disrupting their physiological activity and leading to cell death. The effects of AgNPs on bacterial DNA were not analyzed in detail with respect to possible DNA lesions and antibacterial action that occur after AgNPs treatment. Silver nanoparticles exert their bactericidal activity through a Trojan-horse mechanism, since their initial binding to the cell surface leads to permeability alteration and cellular respiration impairment, followed by cell-barrier penetration and intracellular metallic silver ion release. In order to successfully apply nanosilver-based systems as effective antibacterial agents, it is important to thoroughly understand their action against bacterial cells and bacterial biofilms [72]. In addition to their improved efficiency against planktonic bacteria (as discussed above), AgNPs also possess bactericide or bacteriostatic activity against biofilm-organized microorganisms. The antibacterial effects exhibited by silver-based nanosystems against biofilm-organized bacteria may be due to intrinsic activity against isolated or block cells, destabilization or disruption of the exopolymeric substances within the extracellular biofilm matrix, or interfering with bacterial signaling molecules [73–75]. There are ongoing discussions regarding the role of Ag ions released from AgNPs and their related toxic effect on microorganisms. Many researchers stated that the toxicity of AgNPs is due to the nanoparticles themselves, whereas others provided evidence that silver ions released from AgNPs play a crucial role during antimicrobial activity. Following the release of silver ions from AgNPs, antibacterial activity is initiated by metallic cations, rather than by metallic nanoparticles [76]. 3. Silver Nanoparticles for Drug-Delivery Systems In medicine, the pharmacokinetics and pharmacodynamics of drugs are as important as their intrinsic therapeutic effects [77]. Since the specific and selective delivery and action of therapeutic agents became one of the most studied topics for improving current human healthcare practice, nanoparticles received tremendous attention regarding the design and development of novel and enhanced drug-delivery systems [78]. In particular, AgNP-based nanosystems were evaluated as suitable carriers of various therapeutic molecules, including anti-inflammatory [79,80], anti-oxidant [81,82], antimicrobial [83,84], and anticancer [32,85] biosubstances. In order to provide a specific therapeutic effect in human or animal organisms, it is essential to consider the process or method applied during the administration of the selected pharmaceutical compound [86]. For obtaining novel and performance-enhanced drug-delivery systems responsive to thermal, optical, or pH modulations to target inflammatory, infectious, and malignant ailments, hybrid molecular units consisting of AgNPs were successfully chosen, especially thanks to their exceptional biocompatibility and viable features for nanoscale-derived therapeutic settings [87]. As a consequence of the difficulty encountered during AgNP synthesis and the concerns regarding the toxicity and reduced stability of nanosilver-based systems when functionalized according to conventional salt-aging techniques, silver is not extensively used in nanoparticle-based drug-delivery applications, instead being replaced with gold or other nanomaterials [88]. An excellent triggerable and tunable nanosystem for drug-delivery applications should be easy to develop from readily available components, exhibit optimal responsiveness, and be compatible with more than one trigger [89]. Moreover, such a particular drug-delivery [90] platform should not only provide suitable andPDF Image | Biomedical Applications of Silver Nanoparticles
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