Marine-derived carbon dots: a safe and effective solution for noise-induced hearing loss.

Noise-induced hearing loss (NIHL) remains highly prevalent in occupational settings, and no pharmacological agent or combination thereof has demonstrated a protective or restorative impact against noise-induced damage in clinic till now. Biomass-derived carbon dots (CDs) are known for their unique biological activities and excellent safety. Marine organisms account for 78% of the planet's biomass. In this vast and diversified habitat, marine animals make and gather significant amounts of compounds with distinct structural and physiological properties. Here, using eight different marine fauna and flora as carbon sources, safe and green CDs were synthesized through one-pot hydrothermal method. All eight CDs displayed good stability and radical quenching abilities. In ABR testing, the Undaria pinnatifida Suringar-derived CDs (USCDs) exerted the strongest hearing protection abilities under noise exposure in vivo among the eight samples. The structure-activity relationships of marine-derived CDs suggested that improved content of heteroatom or reductive function groups was essential for their radical scavenging and in vivo anti-NIHL activities. The cytoprotective activity for auditory nerve and hair cells in vivo were confirmed by confocal microscopy. Notably, in vitro cell tests demonstrated that USCDs could prevent apoptosis and ferroptosis through ROS scavenging and Fe2+-chelating, respectively. Moreover, both in vivo and in vitro experiments demonstrated that USCDs possessed excellent biosafety and blood-labyrinth barrier (BLB) permeability, supporting their potential for systemic administration. These findings broaden the potential applications of CDs in the treatment of inner ear diseases, and provided some insights into the development marine drugs.