AS1411适配体靶向氧化钆相关纳米载体的构建在肾癌磁共振分子成像中的研究

Renal cell carcinoma (RCC) is high degree of malignancy and its incidence is increasing. Early diagnosis of RCC and detection of micrometastases are important and difficult in clinical diagnosis and treatment. In our group, we previously constructed N-palmitoyl glucosamine modified Gd-DTPA-containing polyethylene-glycolated liposome (NPG-PEG-Gd-DTPA liposome) and realized its in vitro and in vivo application in RCC tumor imaging. Based on this, in order to further improve the sensitivity and selectivity of MRI, we plan to prepare mMRI nanoprobe by layer-by-layer assembly, in situ synthetic approach as well as covalent couping method and realized the mMRI diagnosis of renal carcinoma both in vitro and in vivo. This mMRI probe integrates aptamer as targeting molecule, gadolinium oxide nanoparticles as contrast agent and porus silica or graphene oxide as nanocarriers. With the preparation of nanocarriers, the contrast ability of nanoprobe and the sensitivity of MRI would be improved greatly. Additionally, nanoporus materials and nano-sheet structure favors the functionalization of targeting molecules and fabrication of drug carrier. This would provide imaging basis for the application of molecular imaging in cancer diagnosis and treatment.

肾癌恶性程度高且发病率呈上升趋势，肾癌早期诊断及微小转移灶的检测是目前临床诊疗的重点与难点。本项目前期制备了葡萄糖受体靶向Gd-DTPA长循环脂质体，在实现肾癌细胞的体外靶向检测和裸鼠肾癌移植瘤的体内靶向诊断的基础上，为进一步提高MR靶向成像的敏感性和选择性，拟以Gd2O3纳米粒子作为对比剂、纳米多孔二氧化硅和氧化石墨烯为载体、核酸适配体为靶向识别分子，通过层层组装、原位合成和共价结合作用构建磁共振分子成像纳米探针，初步实现mSiO2@Gd2O3对肾癌细胞的体外灵敏靶向和裸鼠肾癌移植瘤的在体MR分子成像。通过纳米载体的构建，增强纳米分子探针的对比度，提高MR成像的敏感性，纳米多孔材料和纳米片层结构更易于进行表面靶向功能化和载药模型的构建，为MRI分子影像在肿瘤诊疗研究提供影像学基础。

肾癌恶性程度高且发病率呈上升趋势，肾癌早期诊断及微小转移灶的检测是目前临床诊疗的重点与难点。在本项目中，我们以Gd2O3纳米粒子作为对比剂、纳米多孔二氧化硅和氧化石墨烯为载体、核酸适配体为靶向识别分子，通过层层组装、原位合成和共价结合作用构建磁共振分子成像纳米探针mSiO2/PSS/PDDA/BSA-Gd2O3/AS1411和GO/BSA-Gd2O3/AS1411-DOX诊疗一体化纳米探针，对肾癌细胞的体外灵敏靶向及治疗和裸鼠肾癌移植瘤的在体MR分子成像。通过纳米载体的构建，增强纳米分子探针的对比度，提高MR成像的敏感性，纳米多孔材料和纳米片层结构更易于进行表面靶向功能化和载药模型的构建，为MR I分子影像在肿瘤诊疗研究提供影像学基础。