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INTRODUCTION: Human exposure to nanoparticles is increasing due to their widespread use in industry and consumer products. The unique physicochemical properties of these materials lead to novel toxicological effects, primarily driven by the induction of oxidative stress and inflammation, establishing nanotoxicology as a critical public health field. This scoping review synthesizes the current evidence from preclinical models to provide an overview of the mechanisms and end-organ toxicities associated with exposure to metal-containing nanoparticles. METHODS: A scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The PubMed database was searched on August 11, 2024, using a detailed search string focused on nanoparticle inhalation, human toxicity, and metals. Inclusion criteria specified English-language articles reporting on in vivo or in vitro human tissue studies, while studies that were animal-only, reviews, or non-toxicological modeling were excluded. RESULTS: The initial search yielded 946 records; ultimately, 136 articles were analyzed based on the inclusion and exclusion criteria. A thematic analysis of the included studies reveals that research is heavily concentrated on the respiratory, gastrointestinal, and immune systems, with titanium dioxide and zinc oxide being the most frequently investigated nanoparticles. Across all organ systems, the principal mechanisms of toxicity were consistently identified as the generation of reactive oxygen species and the initiation of inflammatory cascades. Key organ-specific findings include disruption of the respiratory epithelial barrier, nanoparticle translocation to the cardiovascular and nervous systems, associated mitochondrial damage and protein aggregation, and dose-dependent genotoxicity, including DNA strand breaks and micronuclei formation. DISCUSSION: The toxicity of metal-containing nanoparticles is highly dependent on their specific physicochemical characteristics, including size, chemical composition, and agglomeration state. While in vitro models have been invaluable for elucidating these mechanistic pathways, significant limitations remain, including a lack of standardization and challenges in translating findings to clinical outcomes in humans. Future research should focus on validating advanced, reproducible models, investigating complex mixed exposures, and identifying sensitive biomarkers to better inform risk assessment and protect public health. CLINICAL TRIAL NUMBER: Not applicable.
Miller et al. (Tue,) studied this question.