Evaluating the nanotoxicity and antioxidant pathway modulation of MnO2 nanoparticles in zebrafish

Abstract Metal oxides-particularly MnO 2 nanoparticles (NPs)-have shown great promise due to their unique physicochemical properties, such as biocompatibility, catalytic activity, stimulus-responsiveness, Fenton-like reactivity, and enzyme-mimicking behavior. Nonetheless, applying MnO 2 NPs in vivo continues to raise concerns about their toxicity and biological impacts on organisms. In this study, MnO 2 NPs were synthesized via a simple one-pot method by directly mixing potassium permanganate (KMnO 4 ) with poly(allylamine hydrochloride) until complete conversion was achieved, followed by characterization of their physical and chemical properties. The toxicity of MnO 2 NPs was observed by analyzing morphological changes, mortality rates, and gene expressions. The morphological development of zebrafish after being treated with MnO 2 NPs at concentrations of ≤ 0.1 mg/mL indicated that the material was largely biocompatible with early zebrafish embryogenesis. Mortality data demonstrated that a low concentration (0.025 mg/mL) of MnO 2 NPs was relatively safe, while higher doses (≤ 0.1 mg/mL) may impair survival due to cumulative oxidative stress or related nanotoxicity effects. Meanwhile, a qPCR analysis revealed that at high MnO 2 NP concentrations, expressions of sod1 and sod2 increased, but cat and gpx1 expressions remained relatively stable, indicating that MnO 2 NPs act directly as an H 2 O 2 detoxification agent and maintain cell homeostasis without causing zebrafish death at low concentrations.