Surface HEI-OC1-Engineered Magnetic Nanoparticles with Antioxidant Coatings Mitigate Ototoxic Stress in HEI-OC1 Auditory Cells

Hearing loss represents a major global health challenge. Particularly, ototoxicity induced by cisplatin and aminoglycosides remains a significant clinical problem. In this study, we synthesized and characterized magnetite nanoparticles (Fe₃O₄) functionalized with protocatechuic acid (Fe₃O₄@3,4-DHAB) and with protocatechuic acid plus sodium citrate (Fe₃O₄@3,4-DHAB@NaCitrate) and evaluated their effects on auditory House Ear Institute-Organ of Corti 1-(HEI-OC1) cells exposed to cisplatin and gentamicin. The nanoparticles exhibited good biocompatibility, maintaining a cell viability above 85% even at high concentrations. Functionalized formulations, particularly Fe₃O₄@3,4-DHAB, mitigated drug-induced loss of viability, preserved mitochondrial membrane potential, and reduced senescence-associated activity. These protective effects are consistent with the intrinsic antioxidant and anti-inflammatory properties of protocatechuic acid. Although limited to an in vitro model, our findings provide preliminary evidence that rational surface engineering of magnetic nanoparticles represents a viable strategy for mitigating ototoxic stress. This study builds upon our previous work demonstrating the role of PCA-functionalized Fe₃O₄ nanoparticles in modulating immune responses and promoting interactions with adipose-derived stem cell phenotypes. Together, these results underscore the potential of multifunctional nanomaterials to contribute to the development of novel approaches for hearing preservation.