We disclose herein the first example of stable monodispersed hybrid nanoparticles (termed MelaSil-NPs) made up of eumelanin biopolymer intimately integrated into a silica nanoscaffold matrix and endowed with high antioxidant and cytoprotective effects associated with a specific subcellular localization. MelaSil-NPs have been fabricated by an optimized sol-gel methodology involving ammonia-induced oxidative polymerization of a covalent conjugate of the eumelanin building block 5,6-dihydroxyindole-2-carboxylic acid (DHICA) with 3-aminopropyltriethoxysilanes (APTS). They displayed a round-shaped (ca. 50-80 nm) morphology, exhibited the typical electron paramagnetic resonance signal of eumelanin biopolymers, and proved effective in promoting decomposition of hydrogen peroxide under physiologically relevant conditions. When administered to human ovarian cancer cells (A2780) or cervical cancer cells (HeLa), MelaSil-NPs were rapidly internalized and colocalized with lysosomes and exerted efficient protecting effects against hydrogen peroxide-induced oxidative stress and cytotoxicity.
Keywords: antioxidant; cytoprotection; eumelanins; hybrid nanomaterial; lysosomal localization; oxidative stress; silica nanoparticles.