Subcellular-Level Physiological Cisplatin Distribution in the Cochlea

Cisplatin ototoxicity (CO) contributes to ~0.5 million hearing impairment cases among cancer patients globally each year. The lack of understanding of cisplatin distribution in the cochlea and the mechanism of CO hinders the development of effective prevention and treatment strategies. Recently, our group reported a promising candidate, honokiol, for treating CO during chemotherapy. Whether honokiol works through affecting cisplatin distribution is neither clear. 2D sections of cochleas can provide some clues on Pt distributions, however, we need a comprehensive understanding on the three-dimensional (3D) cisplatin distributions within the cochlea internal network.Therefore, we want to perform correlative holographic nanotomography and 3D XRF scanning on vitrified cochleas for precise and comprehensive observation on Pt targeted subcellular compartments. This research will provide crucial insights for understanding the mechanism of CO and the protective effect of honokiol.