宫颈癌是最常见的妇科恶性肿瘤之一，放射治疗是宫颈癌的主要治疗手段。然而肿瘤组织具有特殊的微环境，如乏氧、谷胱甘肽含量高、酸性pH和过氧化氢过剩等，显著影响着肿瘤对放射治疗的抵抗性，肿瘤放疗疗效仍有待提高。因此探寻新的方法，提高宫颈癌的放射治疗疗效，是亟待解决的问题。本课题前期研究发现，FePt纳米材料具有放疗增敏作用。基于前期研究结果和MnO2的催化过氧化氢和谷胱甘肽消耗特性，本课题拟设计一种新型壳核结构的FePt@MnO2纳米材料，构建集肿瘤细胞杀灭与正常细胞保护于一体的特异性放疗增敏探针。该探针可实现在肿瘤部位的特异性响应，同时降低肿瘤组织内谷胱甘肽和过氧化氢的含量，改善乏氧环境，降低活性氧的消耗，从而增强放疗疗效。本研究拟利用纳米探针、肿瘤微环境和放射治疗三者之间的相互作用关系达到提高肿瘤治疗效率，并探讨细胞的凋亡机制，为提高肿瘤疗效提供新的技术手段和理论基础。

Cervical cancer is one of the most common gynecological malignancies worldwide and radiotherapy(RT) plays a major role in the treatment of patients undergoing cervical cancer. However, the therapeutic efficacy remains to be improved due to the radiation resistance, which significantly affected by the tumor microenvironment (TME). TME often featured by hypoxia, acidic extracellular matrix, overproduced H2O2 and GSH, can dictate aberrant tissue functions and promote tumor progression. Therefore, developing new methods to effectively coordinate with radiotherapy to improve the outcomes is extremely urgent and desirable. Our preliminary study found that FePt nanoparticles exhibited enhanced sensitivity to radiotherapy. Herein, we design an all-in-one FePt@MnO2 nanoprobe that integrates TME-response and RT into one system for high efficient therapy of cervical cancer. On one hand, the EPR effect, together with the pH/GSH/H2O2-responsive dissociation of MnO2 shell, allows the nanoprobe to aggregate and release at the tumor site. On the other hand, due to the intrinsic catalase-like activity and GSH consumption properties, the FePt@MnO2 nanoprobe could serve as a smart agent to achieve remarkable inhibition of tumor growth by promoting O2 generation and intracellular ROS production. In this way, the well-defined FePt@MnO2 nanoprobe not only can modify the hypoxic condition but also induce cell apoptosis significantly through ROS-mediated mechanism, thereby resulting in enhanced RT cancer. The aim of our study is to evaluate the efficacy of the combination therapy and explore the possible apoptosis mechanisms. It is hoped that the GSH-depleting and O2/ROS production strategy developed in this work can provide a new strategy for designing radiosensitizers and will find potential applications in improving the therapeutic effect of cervical cancer.