顺铂是临床常用的广谱抗癌药物，对治疗多种癌症具有突出的疗效。然而，顺铂化疗造成的耳毒性却严重降低了癌症患者的生活质量，尤其影响儿童早期语言发育和社会认知能力。本项目从治疗顺铂化疗诱导的听力损失的临床需求出发，以获得低毒高效的治疗药物为目标，设计和合成系列生物可降解双亲性高分子，高分子或自身可与顺铂螯合，或通过化学键合可与顺铂螯合的药物形成双亲性高分子药物的键合物，并进一步包裹超顺磁氧化铁（SPIO）制备磁性纳米胶束。在外在磁场的介导下，构建基于生物可降解高分子的磁性纳米透析平台用来清除顺铂化疗造成的耳蜗内的药物残留。通过调控磁性纳米胶束的组成、结构及表面性质，优选纳米药物类型，并通过纳米透析法，在动物模型上实现对耳蜗内顺铂的高效清除，增强药物对治疗顺铂诱导听力损失的效果，优化出低毒高效的治疗药物和合理的治疗方案。该项目研究将为纳米载体材料在临床上的转化与应用提供新的思路和方法。

Cisplatin is a widely used anti-cancer drug in clinics, and has outstanding therapeutic efficacy on various types of cancers. However, the ototoxicity of cisplatin severely decreases the patient's quality of life, especially affecting the early language development and social cognitive ability of children. In order to meet clinical needs, the project aims to explore therapeutic drugs with low toxicity and high-efficiency for the treatment of cisplatin-induced hearing loss. We proposed to design and synthesize a series of biodegradable amphiphiles polymers, which can chelate with cisplatin by itself, or through chemical bonding with cisplatin-chelating drugs to form amphiphilic polymer-drug conjugate. Next, superparamagnetic iron oxide (SPIO) will be encapsulated into these amphiphic polymer/polymer-drug conjugate to prepare magnetic nanomicelles. With an external magnetic device, an inner ear nanodialysis detoxification platform based on biodegradable polymers will be developed to remove drug residues in the cochlea caused by cisplatin chemotherapy. The nanosized micelle will be optimized by adjusting its composition, structure and surface characteristics for the further in vivo study. Through the nanodialysis platform, the cisplatin in the cochlea will be effectively sequestered. As a result, it will enhance the therapeutic effect in an animal model with cisplatin-induced ototoxicity in clinical settings. On this basis, the low-toxic and high-efficiency therapeutic drugs and reasonable treatment method can be optimized. If this innovative system proves effective and safe, the project will provide new ideas and methods for the clinical transformation and application of nanocarriers.