米索硝唑(MISO)是第一个经临床广泛研究的乏氧细胞放射增敏剂，其放射增敏比（SER）优于甘氨双唑钠，且随剂量增加可进一步提高，因其对外周神经组织的毒性限制了使用剂量，使其Ⅲ期临床试验失败。本课题采用脂质体技术将MISO包裹在 pH敏感脂质体的疏水层，将无放射性的显影剂--超顺磁氧化铁纳米粒（SPIO）包裹在亲水层，制得MISO靶向脂质体。利用pH敏感脂质体仅在低pH环境下释药，及实体瘤间质处的pH值（6.5）低的特点，以提高肿瘤组织中MISO的药物浓度，从而进一步增加SER、降低外周神经组织毒性，并通过SPIO于磁共振下显像示踪证实肿瘤靶向性。预试验表明该脂质体具有高度的pH敏感性及荷瘤鼠肿瘤内的靶向性。本课题拟进一步优化MISO靶向脂质体的处方、克服制备工艺的难题，并在荷鼻咽癌、食管癌、肺癌的荷瘤鼠体内验证进一步提高的SER及降低的外周神经组织毒性，为MISO再次进入临床打下基础。

Misonidazole (MISO), the first hypoxic cell radiosensitizer, has been in clinical trials for decades. MISO is more efficient than sodium glycididazole, i.e., its adiosensitization ratio (SER) is higher and it can produce a greater amount of sensitization for a higher dose. However, the dose of MISO is limited by the peripheral neurotoxicity, discouraging the phase III trials. It is well-known that the interstitial substance of solid tumor has a low pH value in 6.5. Our study design based on the data that the drug packed in the pH-sensitive liposome only could be released in a low pH environment. We presumed that the MISO can be concentrated in the tumor by the pH-sensitive liposome, which increasing SER and decreasing the peripheral neurotoxicity. As a tracer, the contrast agent without radioactive--superparamagnetic iron oxide nanoparticles (SPIO) will be used to follow MISO targeting liposome under magnetic resonance imaging. In our study, the preparation of MISO targeting liposome is as follows: the MISO and the SPIO will be packed in the hydrophobic and hydrophilic layers of pH- sensitive liposome, respectively. In our initial studies, these highly pH-sensitive liposomal vesicles can be specially targeted to tumor in bearing mice. In next study, we aim to optimize the prescription and improve the preparation process of the MISO targeting liposome. The nude mice bearing nasopharyngeal carcinoma, esophageal cancer or lung cancer will be used to measure SER and the peripheral neurotoxicity of MISO targeting liposome. This study will provide theoretical evidence for MISO targeting liposome in clinical treatment.