Mechanisms of Cardiovascular Toxicity Induced by Silver Nanoparticles: A Systematic Review of Preclinical Evidence

Clinical Snapshot

Key Findings

• P Value: Not reported at review level; individual study p-values not synthesised

• Effect Size: Not quantified; no pooled effect sizes reported. Qualitative consistency of cardiotoxic findings across 38 preclinical studies is described

• Primary Outcome: AgNP exposure consistently induces cardiovascular toxicity in preclinical models through oxidative stress, mitochondrial dysfunction, DNA damage, and ion channel disruption, manifesting as bradycardia, AV conduction block, impaired contractility, endothelial activation, and vascular dysfunction

• Nnt Or Sensitivity: Not applicable; no quantitative synthesis. Dose-, time-, and size-dependent relationships described qualitatively. Elevated cardiac biomarkers (CK-MB, BNP, LDH) and histopathological changes (pericardial oedema, myofibril disorganisation, fibrosis, inflammatory infiltration) reported as consistent findings across included studies

• Confidence Interval: Not reported; no meta-analytic synthesis performed

Clinical Application

Clinical translation is currently not feasible based on this evidence alone. The mechanistic pathways identified (oxidative stress, ion channel disruption, endothelial activation) are plausible in humans but require validation in human pharmacokinetic studies and epidemiological cohorts before clinical risk thresholds can be established In Australia, AgNP-containing products (wound dressings, antimicrobial coatings, consumer goods) are regulated by the TGA under the Therapeutic Goods Act 1989 and the Industrial Chemicals Act 2019 via AICIS (Australian Industrial Chemicals Introduction Scheme). Safe Work Australia has not established specific occupational exposure limits for AgNPs, though general nanoparticle guidance applies. The RACGP has no specific guidelines on AgNP cardiovascular risk. This review supports the precautionary principle in clinical use of AgNP-containing medical devices, particularly in patients with pre-existing cardiovascular disease. Clinicians should be aware of AgNP exposure in patients using silver-containing wound care products (e.g., Mepilex Ag, Aquacel Ag — not PBS-listed for cardiovascular indications) and consider cardiovascular monitoring in high-exposure scenarios pending human evidence. The findings are directly applicable only to preclinical (animal and cell culture) models. Indirect relevance exists for humans with occupational or medical-device-related AgNP exposure, including patients with AgNP-containing wound dressings, catheters, or implants, and workers in nanomaterial manufacturing or healthcare settings

Abstract

Silver nanoparticles (AgNPs) have emerged as one of the most widely used nanomaterials in medical and consumer products, yet their cardiovascular safety remains inadequately characterized. While their antimicrobial properties are well-documented, accumulating evidence reveals that AgNPs pose a significant threat to the cardiovascular system. Exposure to AgNPs through inhalation, ingestion, or dermal contact enables these particles to enter systemic circulation, where they accumulate in cardiac and vascular tissues in a dose-, time-, and size-dependent manner. Once deposited, AgNPs initiate a cascade of pathological events, including oxidative stress, mitochondrial dysfunction, DNA damage, and disruption of calcium and sodium channel signaling. These molecular disturbances translate into physiological alterations such as bradycardia, atrioventricular conduction block, impaired contractility, and exacerbated ischemia-reperfusion injury. AgNPs also trigger endothelial activation, leading to upregulation of adhesion molecules, namely vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and recruitment of inflammatory cells, creating a proinflammatory and prothrombotic environment. Elevated cardiac biomarkers, including creatine kinase-MB fraction (CK-MB), brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), and histopathological changes, including pericardial edema, myofibril disorganization, fibrosis, and inflammatory infiltration are consistently observed. Vascular dysfunction manifests as impaired vasorelaxation, enhanced vasoconstriction via endothelin-1 upregulation, thrombosis, and abnormal angiogenesis driven by vascular endothelial growth factor (VEGF) dysregulation. Although plant-based AgNPs have shown cardioprotective potential in limited studies, the overall evidence indicates significant cardiovascular risk. This systematic review synthesizes findings from 38 preclinical studies (35 in vivo, 3 in vitro), providing a comprehensive analysis of AgNP-induced cardiotoxicity with emphasis on oxidative stress, inflammation, and molecular dysregulation as core mechanistic drivers.

References

1. 1.Aditya, M. R., Hogipranata, M. O., Adriansyah, V., Muhammad, A. R., Baheera, K. D., Simanjuntak, A. M. T., Rahimah, A. F., Kamila, P. A., & Sulistomo, H. W. (2026). Mechanisms of cardiovascular toxicity induced by silver nanoparticles: A systematic review of preclinical evidence. Frontiers in Medicine. https://doi.org/10.3389/fmed.2022.867497