Hybrid Se/melanin-like nanoparticles as ROS quenchers and inhibitors of amyloid aggregation

: Hybrid selenium/melanin-like nanoparticles offer different therapeutic strategies against amyloid aggregation. In this study, novel Se-based nanostructures are synthesized, characterized, and preliminarily employed as modulators of amyloid aggregation. In detail, two types of Se NPs are tested: one containing only Se(0), named Se NPs, and the second hybrid Se/melanin structures, indicated as SeMel NPs. Advanced biophysical and spectroscopic analyses elucidate the structures of NPs and the mechanistic underpinnings of the inhibition of aggregation of two protein fragments employed as amyloid models, Aβ21-40 and NPM1264-277. Both NPs are investigated for their antioxidant and superoxide dismutase (SOD)-like activity, as well as for their colloidal stability through dynamic light scattering (DLS) and ζ-potential measurements. ThT and SEM experiments demonstrate their ability to suppress amyloid aggregation, while far-UV circular dichroism (CD) spectroscopy indicates secondary structure alterations upon nanoparticle interaction, revealing a shift from β-sheet-rich conformations towards α-helical intermediates. Finally, SeMel NPs demonstrate cytocompatibility with SH-SY5Y cells and an effective mitigation of the cytotoxic effects of the amyloid models. These findings position hybrid Se-melanin NPs as promising agents for targeted amyloid therapeutics.