Nanosilver in Biomedicine: Advantages and Restrictions

Abstract

Nanosilver (in a range 1–100 nm) binds with thyol-, amino- and carboxy-groups of aminoacid residues of proteins and nucleic acids, thus providing inactivation of pathogenic multidrug-resistant microorganisms. Besides antibacterial, antiviral, antifungal and anti-cancer properties Ag-based nanomaterials possess anti-inflammatory, anti-angiogenesis and antiplatelet features. Drug efficacy depends on their stability, toxicity and host immune response. Citrate coated Ag nanoparticles (NPs) remain stable colloid solutions in deionized water but not in the presence of ions due to replacement of Ag+ by electrolyte ions, potential formation of insoluble AgCl, subsequent catalyzed oxidative corrosion of Ag and further dissolution of surface layer of Ag2O. Protein shells protect core of AgNPs from oxidation, dissolution, aggregation and provide specific interactions with ligands. These nanoconjugates can be used for immunoassays and diagnostics but the sensitivity threshold does not exceed 10 pg Cytotoxicity of AgNPs conjugated with proteins is associated with the rate of intracellular Ag+ release, a ‘Trojan horse’ effect, and exceeds one of Ag+ because of endocytosis uptake of NPs but not ions. Relatively toxic nanosilver causes immunosuppression of the majority of cytokines with a few exceptions (IL-1β, G-CSF, MCP-1) whereas AgNO3 additionally activate TNFα and IL8 gene expression.

Targeting of Silver Cations, Silver-Cystine Complexes, Ag Nanoclusters, and Nanoparticles towards SARS-CoV-2 RNA and Recombinant Virion Proteins

“…Nanosilver may be applied for disinfection, inactivated vaccine production, and combined therapy without a risk of pathogen resistance due to the multiple mechanisms of action [ 1 , 3 ] and allergic complications for hosts because of nanosilver-induced immunosupression [ 20 , 21 ]. Cellular uptake of nanosilver may mainly induce T-helper 1 cellular immune response necessary for elimination of intracellular pathogens.…”

“…Protein surface shells protected Ag NPs from dissolution and aggregation. Therefore, the nanoconjugates of the noble metal NPs with proteins remained stable for several months at 4 °C [ 5 , 20 , 21 ].…”

“…The cytotoxicity of Ag nanoconjugates with IgG essentially exceeded that of AgNO 3 ( Table 1 ), perhaps due to the cellular uptake of silver nanostructures covered with IgG but not Ag + ions. The subsequent “Trojan horse” results in high Ag + intracellular concentration and interaction with proteins, nucleic acids, and membranes [ 1 , 3 , 20 , 21 ].…”

“…Partial RNA cleavage in the presence of Ag NPs ( Table 2 ) can be caused by the NPs’ dissolution in the presence of polyanion RNA with Ag + release. Silver ions are known to destroy nucleic acids ([ 20 , 21 ] and references therein).…”

“…Ag NPs exhibit antiviral activity against influenza A virus [ 8 , 9 , 10 , 11 , 12 ], respiratory syncytial virus [ 13 , 14 ], hepatitis B virus [ 15 ], monkeypox virus [ 16 ], vaccinia virus [ 17 ], human parainfluenza virus [ 18 ], herpes simplex virus [ 6 , 18 ], and human immunodeficiency virus (HIV) type 1 [ 19 ]. Despite extensive research and proven antiviral properties, the implementation of nanosilver in commercial antiviral drugs is limited [ 2 , 20 , 21 , 22 ]. Cytotoxicity is a major limitation for their use as antiviral agents in biomedical applications [ 23 ].…”