基于钆金属富勒烯的高效肿瘤诊疗探针的构筑及性质研究

Tumor theranostic nanoprobe can be combined with a variety of molecular imaging modality techniques to achieve a more accurate clinical diagnosis, and could be also combined with therapeutic methods to ultimately to achieve the purpose of personalized therapy. Furthermore, in recent years, fullerenes and endohedral metal fullerenes with unique structure and excellent physical and chemical properties and also withlow toxicity and metabolized advantages，have broad applications in the biomedical field. Moreover, gadofullerenes could be used to enhance the efficiency of magnetic resonance imaging, which is more than 10 times higher than the commercial contrast agent, and they are better for establishing nanoprobes for tumor theranostics as to be easily functionalized. In this project, a versatile and high efficiency nanoprobe was designed and synthesized based on Gd@C82 for high efficiency tumor diagnosis and therapeutics. It not only combined magnetic resonance imaging with fluorescence imaging for high sensitivity diagnosis, but also greatly improved the effects of photodynamic therapy. The project will be included with material preparation, structure characterization, cell experiment and in vivo experimental aspects, to study the key points during tumor theranostics of this gadofullerene based nanoprobe, which lay the foundation for the development novel nanotechnology for tumor diagnosis and treatment.

肿瘤诊疗纳米探针将成像技术与治疗手段融于一体，是实现肿瘤诊疗一体化的关键。富勒烯及金属富勒烯衍生物具有奇特的结构和优异的物理化学性质，并且低毒可代谢，在生物医学领域具有广阔的应用前景。特别是钆金属富勒烯可以作为高效磁共振造影剂，可显著提高磁共振成像分辨率，比商用造影剂的造影效率高10倍以上；并且钆金属富勒烯表面易修饰，为诊疗体系的构筑提供了良好平台。本申请拟针对肿瘤诊疗一体化的需求，将钆内嵌金属富勒烯Gd@C82作为纳米载体，通过偶联光动力治疗试剂构筑一种集实时诊断与高效治疗于一体的多功能纳米探针。该纳米探针不仅将磁共振成像与近红外荧光成像结合进行多模态诊断，同时还可以实现高效的光动力治疗。本项目将通过材料制备、结构表征、细胞实验以及活体实验几个方面展开，研究纳米探针肿瘤诊疗一体化研究中的关键问题，为发展新型肿瘤诊疗纳米探针奠定基础。

近年来癌症的发病率和死亡率均呈上升趋势，每年全球新增癌症患者多达1500万人，严重地威胁着人类的健康。肿瘤的早期诊断与治疗是提高其治愈率及改善患者生存质量的关键。如何实现癌症的早期高灵敏诊断以及高效肿瘤治疗一直是困扰科学界的难题。本申请计划针对肿瘤诊疗一体化的需求，将钆内嵌金属富勒烯Gd@C82作为纳米载体，通过偶联光动力治疗试剂构筑一种集实时诊断与高效治疗于一体的多功能纳米探针。按照计划完成了多功能钆金属富勒烯基诊疗纳米探针的制备和结构性质表征，并在细胞和活体水平实现了诊断与治疗一体化的研究。我们发展了一种基于富勒烯的高效磁共振成像探针PC61BA-(Gd-DO3A)/HSA，用于高灵敏度靶向性肿瘤诊断；发展了一种基于金属富勒烯的纳米探针，其具有高效的自由基清除特性，可以用于和自由基相关的疾病防治中；构筑金属富勒烯纳米颗粒，用于肿瘤血管阻断治疗；构筑不同尺寸的金属富勒烯纳米颗粒，借助其光动力治疗特性，实现了活体水平肿瘤血管阻断治疗。本项目将通过材料制备、结构表征、细胞实验以及活体实验几个方面展开，研究纳米探针肿瘤诊疗一体化研究中的关键问题，为发展新型肿瘤诊疗纳米探针奠定基础。