Ramaswamy Bharath, Roy Soumen, Apolo Andrea B, Shapiro Benjamin, Depireux Didier A
Fischell Department of Bioengineering, University of MarylandCollege Park, MD, United States.
Pfizer Inc.New York, NY, United States.
Front Cell Neurosci. 2017 Sep 13;11:268. doi: 10.3389/fncel.2017.00268. eCollection 2017.
Cisplatin (cis-diamminedichloroplatinum) is widely used as a chemotherapeutic drug for genitourinary, breast, lung and head and neck cancers. Though effective in inducing apoptosis in cancer cells, cisplatin treatment causes severe hearing loss among patients. Steroids have been shown to mitigate cisplatin-induced hearing loss. However, steroids may interfere with the anti-cancer properties of cisplatin if administered systemically, or are rapidly cleared from the middle and inner ear and hence lack effectiveness when administered intra-tympanically. In this work, we deliver prednisolone-loaded nanoparticles magnetically to the cochlea of cisplatin-treated mice. This magnetic delivery method substantially reduced hearing loss in treated animals at high frequency compared to control animals or animals that received intra-tympanic methylprednisolone. The method also protected the outer hair cells from cisplatin-mediated ototoxicity.
顺铂(顺二氨二氯铂)作为一种化疗药物被广泛用于治疗泌尿生殖系统、乳腺、肺以及头颈部位的癌症。尽管顺铂能有效诱导癌细胞凋亡,但接受顺铂治疗的患者会出现严重的听力损失。研究表明,类固醇可以减轻顺铂所致的听力损失。然而,如果全身给药,类固醇可能会干扰顺铂的抗癌特性,或者从中耳和内耳迅速清除,因此鼓室内给药时缺乏疗效。在这项研究中,我们通过磁性方式将负载泼尼松龙的纳米颗粒递送至接受顺铂治疗的小鼠耳蜗。与对照动物或接受鼓室内注射甲泼尼龙的动物相比,这种磁性递送方法在高频下显著降低了治疗动物的听力损失。该方法还保护外毛细胞免受顺铂介导的耳毒性。