From inhalation to systemic damage: Decoding the mechanistic cascade of silica nanoparticle-induced multi-organ toxicity.

The increasing use of silica nanoparticles (SiNPs) has raised concerns about their biotoxicity. Since respiratory exposure is the primary route of human exposure to SiNPs, this study systematically investigated their distribution and damaging effects in the lungs, heart, liver, and kidneys following tracheal drip injection. The results demonstrated that SiNPs distribute across these organs and induce mitochondrial damage, endoplasmic reticulum stress, and activate cell death pathways, including apoptosis, pyroptosis, and autophagy. The most significant damage occurred in the middle-dose group (6 mg/kg). The lungs, as the primary target organ, exhibited pronounced fibrotic changes, while fibrotic lesions were also observed in the heart, liver, and kidneys to varying degrees. These findings suggest that the observed injury mechanisms may collectively contribute to chronic inflammation and promote fibrosis. This study provides critical insights into the multi-organ toxicity of SiNPs, offering a foundation for their safety assessment.