Application of self-assembly palladium single-atom nanozyme over polyoxometalates in protection against neomycin-induced hearing loss by inhibiting ferroptosis

作者：Qin Huo, Chen Chen, Jiahao Liao, Qingdong Zeng, Guohui Nie, Bin Zhang · 发表于：Biomaterials · 年份：2024 · DOI：10.1016/j.biomaterials.2024.122665 · 被引用次数：29 · 研究领域：Advanced Nanomaterials in Catalysis、Nanoplatforms for cancer theranostics、Nanocluster Synthesis and Applications

Deafness mainly results from irreversible impairment of hair cells (HCs), which may relate to oxidative stress , yet therapeutical solutions is lacked due to limited understanding on the exact molecular mechanism. Herein, mimicking the molecular structure of natural enzymes , a palladium (Pd) single-atom nanozyme (SAN) was fabricated, exhibiting superoxide dismutase and catalase activity, transforming reactive oxygen species (ROS) into O 2 and H 2 O. We examined the involvement of Pd in neomycin-induced HCs loss in vitro and in vivo over zebrafish. Our results revealed that neomycin treatment induced apoptosis in HCs, resulting in substantial of ROS elevation in HEI-OC1 cells, decrease in mitochondrial membrane potential , and increase in lipid peroxidation and iron accumulation, ultimately leading to iron-mediated cell death. Noteworthy, Pd SAN treatment exhibited significant protective effects against HCs damage and impaired HCs function in zebrafish by inhibiting ferroptosis . Furthermore, the application of iron death inducer RSL3 resulted in notable exacerbation of neomycin-induced harm, which was mitigated by Pd administration. Our investigation demonstrates that antioxidants is promising for inhibiting ferroptosis and repairing of mitochondrial function in HCs and the enzyme-mimic SAN provides a good strategy for designing drugs alleviating neomycin-induced ototoxicity .