Polyol-Functionalized Manganese-Based Nanoparticles: From Insulin Amyloid Inhibition to Nanozyme-Mediated Antioxidant...

Insulin amyloidosis poses challenges in diabetes therapy and biopharmaceuticals handling. Here, functionalized manganese-based nanoparticles (MnCO₃@TEG, MnCO₃@OAm, MnOHCO₃@TEG, MnO₂/Mn₂O₃@TEG, and Mn₃O₄@PG) were synthesized via solvothermal routes and evaluated in vitro using a fresh insulin aspart formulation (NovoRapid) and a separately aged insulin glargine formulation (Lantus). Structural and colloidal characterization (ATR-FTIR, XRD, TGA, DLS, zeta potential) confirmed phase purity and distinct surface profiles. In the fresh insulin aspart system, all nanoparticles extended the nucleation lag phase, with MnCO₃@TEG delaying fibrillogenesis from 21.16 h to 105.41 h. In the aged insulin glargine system containing pre-existing ThT-positive aggregates, small, negatively charged nanoparticles (MnOHCO₃@TEG, Mn₃O₄@PG) re-established a distinct lag phase and suppressed further aggregation. In the ThT decay assays, highly dispersed Mn₃O₄@PG produced the largest decrease in amyloid-associated fluorescence, to ~40% of the initial signal, whereas large clusters (MnO₂/Mn₂O₃@TEG, 624 nm) produced a smaller decrease; limited access arising from steric effects is one possible explanation. Additionally, structural hydroxyl groups and high colloidal stability enabled MnOHCO₃@TEG (-38.7 mV) to exhibit superior catalase-like H₂O₂ scavenging (42.27% inhibition at 250 μg/mL). Overall, fine-tuning nanoparticle size, surface charge, and core composition may offer a promising dual-action strategy for targeting insulin amyloidosis and associated oxidative stress across different stages of fibril formation, while further structural characterization and biological safety studies are needed to establish its therapeutic relevance.