Kayyali Mohammad N, Ramsey Andrew J, Higbee-Dempsey Elizabeth M, Yan Lesan, O'Malley Bert W, Tsourkas Andrew, Li Daqing
Department of Otolaryngology - Head & Neck Surgery, University of Pennsylvania Health System, BRB 1220, 421 Curie Blvd, Philadelphia, PA, 19104, USA.
Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 Skirkanich Hall, Philadelphia, PA, 19104, USA.
J Assoc Res Otolaryngol. 2018 Apr;19(2):123-132. doi: 10.1007/s10162-017-0648-2. Epub 2018 Jan 18.
Cisplatin-induced hearing loss is experienced by a high percentage of patients with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano-construct capable of sequestering extracellular cisplatin was developed to combat this problem. The nano-construct consisted of superparamagnetic iron oxide nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The glutathione-micelles were analyzed at the cellular level and in an organotypic study for safety evaluation. All utilized methods indicated that the micelles do not cause cellular toxicity or organ damage. The micelles' ability to reduce cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin was pre-treated with the novel nano-construct before being added to growing cells. When compared to cells that were exposed to untreated cisplatin, cells in the pre-treated cisplatin group showed a significant increase in cell viability. This clearly demonstrates that the construct is able to protect the cells from cisplatin cytotoxicity and makes it highly likely that the novel nano-construct will be able to play a role in the protection of the inner ear from cisplatin-induced ototoxicity.
接受顺铂化疗的鳞状细胞癌患者中，有很大比例会出现顺铂诱导的听力损失。为了解决这个问题，人们开发了一种能够螯合细胞外顺铂的新型纳米结构。该纳米结构由包裹在聚合物胶束中的超顺磁性氧化铁纳米颗粒（SPIONs）组成，这些胶束由谷胱甘肽二乙酯共轭两亲性二嵌段共聚物形成。对谷胱甘肽胶束进行了细胞水平分析和器官型研究以进行安全性评估。所有使用的方法均表明，这些胶束不会引起细胞毒性或器官损伤。然后在体外模型中探究了胶束降低顺铂诱导的细胞毒性的能力。在将顺铂添加到生长的细胞之前，先用新型纳米结构对其进行预处理。与暴露于未处理顺铂的细胞相比，预处理顺铂组中的细胞活力显著增加。这清楚地表明该结构能够保护细胞免受顺铂细胞毒性的影响，并且这种新型纳米结构极有可能在保护内耳免受顺铂诱导的耳毒性方面发挥作用。
