利用核技术分析并构建金属标记富勒烯多功能纳米材料

The 64Cu2+ cations were used to label the DOTA-metal-fullerenes and RGD/DOX were modified by covalent linkage on the surface of Gd@C82. A novel antitumor multifunctional theranostic nanoparticles based on the Gd @ C82 was explored and researched. The multifunctional nanoparticles were composed of metal fullerene of Gd @ C82 as the carrier and RGD (Arg-Gly-Asp) of targeted tumor molecular, DOX (Doxorubicin) of antitumor drug and chelating agent of DOTA (1,4,7,10-tetraaz-acyclododecane-N,N',N,N'-tetraacetic acid) on the surface of Gd @ C82 naonoparticles. The multifunctional nanoparticles were a complex of tumor targeting, tumor imaging by the diagnosis of magnetic resonance imaging (MRI) and positron imaging (PET). Not only the MRI imaging properties and enhanced permeability and retention effect（EPR）of Gd @ C82 to tumor，but also DOX on the surface of nanoparticles can be used to tumor therapy. Because the nuclear analysis techniques were high sensitivity with metal cations, the synchrotron radiation techniques, positron emission technology and the methods of IEF, CE, HPLC, MALDI-TOP MS, living cell and living imaging in our lab were used to study the multifunctional nanomaterials. he functionalized nanoparticles carried the small molecule drugs for therapy to tumor and tiusse organs can be studied by through the co-localization of MRI and PET double functional imaging tracer and the biocompatibilities, the targeting, the imaging qualities of MRI and PET, and the treatment of tumor were evaluated during the process of targeted therapy of tumor cells, live organs in vivo of the orthotopic transplantation tumor model of human hepatocellular carcinomain in nude mice. These works will be the research foundation of nanometer materials used in the pathology, diagnosis and therapy of cancer for the clinical in the future.

本项目拟采用金属铜离子对DOTA-富勒烯纳米粒子进行标记，进一步表面共价修饰RGD和阿霉素(Doxorubicin，DOX)，构建基于纳米金属富勒烯Gd@C82的多功能诊疗纳米材料。该纳米材料通过Gd@C82和64Cu2+实现磁共振成像（Magnetic Resonance Imaging，MRI）和正电子发射成像（Positron Emission Tomography，PET）的肿瘤成像诊断，通过富勒烯纳米材料的肿瘤高通透性和滞留效效应（Enhanced Permeability and Retention effect，EPR）和DOX实现肿瘤治疗。利用核分析技术对金属的灵敏度高等特点，高分辨率、多层次、高准确度的研究纳米材料与细胞的相互作用，研究构建的多功能诊疗纳米材料与细胞的相互作用、纳米材料微区分布和探讨其活体代谢过程，实现纳米材料的活体多功能成像和活体肿瘤治疗。

针对肿瘤诊断和治疗过程中耐药和转移的难点，本项目以本实验室自制的富勒烯C60为原料，采用氮宾多加成反应制备出新型的C60多氮杂桥水溶性衍生物作纳米载体，通过可控修饰偶联肿瘤靶向分子RGD、肿瘤化疗药物DOX 以及金属离子螯合剂DOTA ，构建一种多功能的金属富勒烯基纳米诊疗颗粒。该纳米组合材料中，纳米载体单元C60 EPR 肿瘤治疗功能，同时，还利用表面修饰的RGD单元进行肿瘤主动靶向，利用DOTA单元螯合64Cu2+进行正电子PET成像，利用DOX单元进行肿瘤化疗。通过PET和荧光成像共定位示踪，系统评价该“诊疗”多功能纳米材料的生物相容性、靶向性、PET/光学成像及肿瘤治疗效果，研究结合DOX药物的功能化纳米粒子对肿瘤细胞和人肝癌裸鼠皮下-肝原位移植瘤模型活体器官靶向治疗的过程。