Long-term toxicity of polydopamine nanoparticles: Organ-specific biological effects and cumulative histopathological changes.

Polydopamine nanoparticles (PDA NPs) are widely studied for biomedical applications such as drug delivery, imaging, and tissue engineering; however, their long-term in vivo biological effects remain insufficiently characterized. The aim of this study was to evaluate long-term toxic effects in rats (n = 140) following 6 and 12 months of exposure to PDA NPs (126 ± 24 nm) administered at three dose levels (50, 100, and 150 mg/kg bw) via single or repeated (monthly) intravenous administration. At predetermined time points, organs were collected for macroscopic and histopathological evaluation to assess dose-, time-, and exposure frequency-related tissue changes. The results suggest that PDA NPs may induce organ-specific histopathological alterations in a dose- and time-dependent manner. The most pronounced changes were observed in the liver, kidneys, pancreas, and heart, particularly at the highest dose level (150 mg/kg bw). Observed alterations included features consistent with chronic tissue injury, such as myocardial fibrosis and renal structural changes, following prolonged exposure. In contrast, no notable histopathological changes were detected in the brain or spleen. Despite these findings, overall survival remained high (94%), and no overt clinical signs of systemic toxicity were observed in most animals. This study provides further evidence of long-term organ-specific effects associated with PDA NP exposure, highlighting dose- and time-related biological responses relevant for their safety evaluation in biomedical applications.