多功能石墨烯纳米系统用于中药抗肿瘤成像研究

The development of non-invasive, in situ, real-time and dynamic imaging analysis method for monitoring anti-tumor process of Traditional Chinese Medicine (TCM) is the key of studying the pharmacology of TCM, looking for drug targets, as well as establishing individualized TCM anti-tumor treatment. However, each imaging modality has its pros and cons, its own unique advantages along with intrinsic limitations, such as insufficient sensitivity or spatial resolution, which make it difficult to obtain accurate and reliable information at the disease site. In this regard, we design multifunctional graphene nanoprobes, which integrate magnetic resonance imaging and optical imaging agents with different properties into multifunctional nanomaterials, allow precise, high contrast, high resolution and fast imaging; in addition, graphene nanoprobes possessing the ability of passive targeting, active targeting and magnetic targeting could accurate position the cancer cell or tumor tissue; graphene nano probes have super capability for anti-tumor TCM loading due to its huge specific surface area, monitor the process of targeted drug delivery and study the anti-tumor mechanism of TCM through synergetic multimodal imaging. The multifunctional graphene nanoprobes loading TCM could be robust analysis method for intracellular tracking, looking for drug targets as well as clarifying the antitumor mechanism of anti-tumor TCM.

建立无创、原位、实时、动态监测中医药抗肿瘤过程的成像分析方法是监测中药体内分布，寻找药物作用靶点以及探索中药抗肿瘤作用机理的关键。利用单一成像技术难以对中医药抗肿瘤过程进行有效监测。为此本项目拟结合纳米技术及石墨烯的突出特点，构建具有磁共振和光学多模态成像功能的石墨烯纳米探针，使之具备不受组织深度限制的高分辨率、高对比度和高灵敏度的快速成像能力；结合石墨烯纳米探针被动靶向、主动靶向和磁靶向的多重靶向能力，以达到对癌细胞或肿瘤组织准确定位的目的；利用石墨烯纳米探针的巨大比表面积高量负载难溶抗癌中药，采用多模态成像技术观察抗癌中药在抗肿瘤过程中的体内释放和分布情况，监测靶向控释长效给药的过程和效果，为寻找中药作用靶点，阐明中医药抗肿瘤作用机理提供必要依据。

活体多模态成像技术能够提供详细的解剖和功能信息，是无创、原位、实时动态监测中医药抗肿瘤过程的有效手段。因此，设计构筑多模式成像探针是获取全面、准确影像信息的关键。本项目以发展新型高效 “诊疗一体化”多功能探针为目标，围绕新型纳米材料制备、新型靶向探针设计和复杂生物体系应用拓展等三个方面，系统开展了基于石墨烯纳米材料功能组装体的细胞、活体层面相关肿瘤诊断与治疗基础研究。主要成果包括：① 搭建了具有荧光和磁共振双模态成像功能的中空核壳结构的给药系统，采用多种表征手段证明该材料的结构以及表面性质，并研究了其在体外和体内的特性。该纳米系统具有良好的稳定性、分散性和低毒性，具备较好的荧光和磁共振成像效果，并能够实现活体小鼠肾脏被动靶向给药。② 利用新型液相激光溶蚀纳米制备技术（Laser ablation in liquid, LAL）一步法制备得到了石墨烯氧化铁纳米诊疗系统，该方法具有制备工艺绿色简单、磁共振成像效果好等优点。该诊疗系统具有比表面积大、稳定性好和无毒的优点，并具有优异的光热转换性能。小鼠活体磁共振和热成像能够对肿瘤治疗过程进行实时监控功能，同时在磁热的作用下，化疗效果得到了明显的增强。③构建了具有肿瘤主动靶向功能的石墨烯氢氧化氧铁纳米诊疗平台，探讨了其信号输出与光热疗效等性能以及与下游靶向功能模块的偶联方法，并考察了其对中药活性成分的负载与释放能力，同时开展了细胞、活体层面肿瘤磁共振成像及其引导下的近红外光热治疗。项目研究成果突破了传统诊疗策略在靶向性、灵敏度和副作用等方面的局限，为发展无创、原位、活体诊断新方法，将对肿瘤早期诊断和治疗、分子影像学、纳米技术和分子工程技术等领域的发展起到积极的推动作用。