Toxicological Effects of Silver Nanoparticles in Biological Systems

Silver nanoparticles (AgNPs) have become ubiquitous in consumer, medical and industrial products owing to their potent antimicrobial properties. However, their nano-scale size and distinctive surface characteristics endow them with a capacity to interact intimately with biological structures, raising concerns regarding unintended toxicological outcomes. Upon entry via oral, intravenous, inhalation or dermal routes, AgNPs may undergo partial dissolution to release silver ions, while intact particles can distribute systematically. Key target organs include the liver, spleen, kidneys, lungs and, to a lesser extent, the brain and testis. Toxic effects arise through multiple mechanisms: induction of oxidative stress via excessive reactive oxygen species; inflammation marked by cytokine release; disruption of cellular membranes and cytoskeleton; genotoxicity leading to chromosomal aberrations; and interference with immune function. Size-dependent behaviour is evident, with smaller particles exhibiting greater tissue penetration, enhanced reactivity and more pronounced hepatobiliary damage. Surface coating and chemical composition modulate both biodistribution and toxicity profiles. Chronic exposure can result in bioaccumulation, especially in tissues protected by biological barriers, and may provoke subtle yet persistent dysfunctions, such as impaired mitochondrial performance and altered autophagic flux. Understanding these multifaceted pathways is crucial for risk assessment and the design of safer nanomaterials.

Research from Nature Portfolio

Comparative in vivo studies have contrasted the biodistribution and toxicity of silver and gold nanoparticles following repeated intravenous administration in murine models. Silver nanoparticles were shown to accumulate preferentially in mononuclear phagocyte system organs, including the liver, spleen, heart and lungs, and to elicit greater changes in gene expression related to oxidative stress and apoptosis than their gold counterparts. These findings underscore the critical influence of chemical composition on nanoparticle kinetics and toxic profiles.

Investigations into microglial processing of citrate-capped silver nanoparticles have revealed an intracellular transformation whereby silver ions are sequestered as silver sulfide on particle surfaces. Concurrent up-regulation of hydrogen sulfide–synthesising enzymes in microglia mitigates reactive oxygen species production, reduces pro-inflammatory cytokine release and limits neuronal toxicity. This work highlights a self-protective mechanism in brain immune cells and offers insight into nanoparticle-induced modulation of neuroinflammation.

Toxicological Effects of Silver Nanoparticles in Biological Systems publication trend

The graph below shows the total number of articles in toxicological effects of silver nanoparticles in biological systems across all publications each year (not limited to Nature Index journals).

Technical terms

Mononuclear Phagocyte System (MPS): A network of macrophages in organs such as liver and spleen responsible for nanoparticle clearance.

Reactive Oxygen Species (ROS): Highly reactive molecules derived from oxygen that can damage lipids, proteins and DNA.

Bioavailability: The proportion of administered material that reaches systemic circulation and is available to tissues.

Genotoxicity: The capacity of a substance to damage genetic information, leading to mutations or chromosomal aberrations.

Lipid Peroxidation: Oxidative degradation of lipids in cell membranes, often used as a marker of oxidative stress.

References

1. Comparative in vivo toxicokinetics of silver powder, nanosilver and soluble silver compounds after oral administration to rats. Archives of Toxicology (2023).
2. In Vivo Pro-Inflammatory Effects of Silver Nanoparticles on the Colon Depend on Time and Route of Exposure. International Journal of Molecular Sciences (2024).
3. Comparisons of the biodistribution and toxicological examinations after repeated intravenous administration of silver and gold nanoparticles in mice. Scientific Reports (2017).
4. Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H2S-synthesizing enzymes. Scientific Reports (2017).
5. Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects. Particle and Fibre Toxicology (2015).
6. A Low Dose of Nanoparticulate Silver Induces Mitochondrial Dysfunction and Autophagy in Adult Rat Brain. Neurotoxicity Research (2020).