Silver Nanostructures: Limited Sensitivity of Detection, Toxicity and Anti-Inflammation Effects

Nanosilver with sizes 1-100 nm at least in one dimension is widely used due to physicochemical, anti-inflammatory, anti-angiogenesis, antiplatelet, antifungal, anticancer, antibacterial, and antiviral properties. Three modes of the nanosilver action were suggested: "Trojan horse", inductive, and quantum mechanical. The Ag⁺ cations have an affinity to thiol, amino, phosphate, and carboxyl groups. Multiple mechanisms of action towards proteins, DNA, and membranes reduce a risk of pathogen resistance but inevitably cause toxicity for cells and organisms. Silver nanoparticles (AgNP) are known to generate two reactive oxygen species (ROS)-superoxide (•O₂^-) and hydroxyl (•OH) radicals, which inhibit the cellular antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and cause mechanical damage of membranes. Ag⁺ release and replacement by electrolyte ions with potential formation of insoluble AgCl result in NP instability and interactions of heavy metals with nucleic acids and proteins. Protein shells protect AgNP core from oxidation, dissolution, and aggregation, and provide specific interactions with ligands. These nanoconjugates can be used for immunoassays and diagnostics, but the sensitivity is limited at 10 pg and specificity is restricted by binding with protective proteins (immunoglobulins, fibrinogen, albumin, and others). Thus, broad implementation of Ag nanostructures revealed limitations such as instability; binding with major blood proteins; damage of proteins, nucleic acids, and membranes; and immunosuppression of the majority of cytokines.