Physicochemical Aspects and Cellular Effects of Nanoceria–Human Serum Albumin Conjugates

Abstract

Nanoceria exhibits unique catalytic properties towards reactive oxygen species (ROS), which act as mediators of key signaling pathways. Albumin is the most abundant blood protein, and its interaction with nanoceria modifies the properties of both nanoceria and albumin. Using an in vitro model of human embryonic lung fibroblasts, we investigated biochemical properties of nanoceria–albumin conjugates towards cell viability, intracellular reactive oxygen species, expression of NOX4, NRF2, and NF-κB, oxidative DNA damage/repair, apoptosis, cell proliferation, and autophagy. The results demonstrate that albumin binding alters the physicochemical properties of nanoceria, promoting efficient cellular uptake through modulation of surface interactions. This conjugation attenuates nanoceria’s influence on intracellular reactive oxygen species equilibrium and mitochondrial membrane potential by modifying nanoparticle-protein interfacial dynamics. Notably, albumin-bound nanoceria induces a stronger activation of NOX4, resulting in increased genotoxic stress; however, the enhanced activation of DNA repair pathways mitigates this damage more efficiently than bare nanoceria. Furthermore, albumin-to-nanoceria conjugation modulates signaling pathways by enhancing suppression of the pro-inflammatory NF-κB cascade and stimulating autophagic processes. Overall, the physicochemical effects of nanoceria modification due to albumin conjugation reduce cytotoxicity of nanoceria while augmenting its anti-inflammatory and regenerative potential.