Cell-inspired dual-tandem catalytic nanoreactors drive targeted hearing protection

Abstract

Sensorineural hearing loss is driven by disruption of cochlear homeostasis, where dysregulated redox, ionic, and metabolic factors lead to hair cell degeneration and synaptic injury. Current strategies lack the capacity to restore the enzymatic clearance of reactive oxygen species or penetrate the blood-labyrinth barrier. Here, we report a cell-inspired dual-tandem catalytic nanoreactor (HSC@Se) integrating GPx-mimetic diselenide with superoxide dismutase and catalase to reconstruct the detoxification cascade. We show that the albumin scaffold stabilizes the nanoarchitecture and enables active blood-labyrinth barrier penetration of neutrophil-adhesive transport and megalin-mediated uptake, facilitating cochlear delivery to hair cells and spiral ganglion neurons. In noise-induced mouse models, we demonstrate that HSC@Se restores redox equilibrium, suppresses ferroptosis, normalizes iron handling, preserves hair-cell integrity, maintains ribbon synapses, and reduces auditory threshold shifts. We perform transcriptomics to reveal activation of antioxidative and metabolic repair pathways. This work presents cell-inspired nanoreactors that emulate natural antioxidant networks to rebalance cochlear redox homeostasis and drive hearing protection.