How do particle size, dosage, and exposure duration influence oxidative stress parameters and the in vivo toxicological profile of polydopamine nanoparticles?

This study assessed the toxicity and changes in oxidative stress biomarkers in plasma and organs of rats treated with manganese-modified polydopamine nanoparticles (PDA@Mn NPs). In vivo MRI experiments demonstrated that our nanoparticles exhibit strong contrast properties with higher efficiency than similar materials reported in the literature. The nanoparticles, available in three sizes (∼50, ∼100, and ∼200 nm), were administered at two dosage levels (15 and 45 mg/kg bw) and assessed at four time points: 1 h, 24 h, 7 days, and 28 days post-administration. A histological evaluation of tissues was conducted. Plasma, liver, and kidney samples were analyzed for oxidative stress biomarkers, including total protein (TP), reduced glutathione (GSH), Trolox equivalent antioxidant capacity (TEAC), nitric oxide (NO), S-nitrosothiols (RSNO), thiobarbituric acid reactive substances (TBARS), catalase (CAT), glutathione S-transferase (GST), and superoxide dismutase (SOD). The analysis has shown that ∼100 nm-sized PDA@Mn NPs appear to be less toxic, whereas both smaller (∼50 nm) and larger (∼200 nm) nanoparticles, particularly at higher doses, induce more intense oxidative stress and organ damage. These findings indicate that the size and dose of PDA@Mn NPs have impact on their toxicity. Therefore, optimizing these parameters is crucial for minimizing toxicity while maintaining therapeutic efficacy in biomedical applications.