The role of natural products in modulating metal nanoparticle toxicity: A review of mechanisms and evidence

Metallic nanoparticles (MNPs) are widely used in medicine, industry, and consumer goods due to their unique nanoscale properties. However, these same features pose potential health risks through mechanisms such as oxidative stress, inflammation, and cellular damage. This review highlights how MNPs interact with biological systems, leading to toxicity that affects DNA, proteins, and organs—particularly the brain, liver, and immune system. Key physicochemical properties, including particle size, surface charge, and exposure route, influence the extent of toxicity. To address these risks, we explore the protective potential of natural products—especially polyphenols, vitamins, and herbal extracts—that counteract MNP-induced damage by scavenging reactive oxygen species and modulating inflammatory pathways. Evidence from in vitro, in vivo, and clinical studies demonstrates the capacity of these compounds to mitigate nanoparticle toxicity. We also discuss the promise of green synthesis approaches to enhance biocompatibility. By integrating knowledge from nanotoxicology and natural pharmacology, this review presents a dual strategy for safer nanotechnology: understanding toxicological mechanisms and applying biocompatible natural mitigators. These insights can guide future design of safer nanoparticles and therapeutic interventions.