多肽介导靶向脑胶质瘤的双模态纳米探针构建及在体成像研究

Glioblastoma（GBM） is the most common malignant brain tumor. Identification of the GBM with current clinical MR probes has limited performance due to their inability to penetrate the well-known blood-brain barrier or BBB. As a result, over 10% of the spongioblastoma and 30% of the astrocytic GBM can not be identified using current technology. In our previous work, using functional self-assembly peptides, fluorescent dye indocyanine monodisperse, and magnetic mesoporous silica nanoparticles, we can construct a new bimodal fluorescence probe which can penetrate the BBB and target the GBM effectively. This proposal aims to explore the methods and techniques for preparing this probe, and moreover, to investigate its characteristics including the biocompatibility in vivo, tumor targeting, and distribution. Succefully carried out, this project expects to reveal the relationships between the probe’s characteristics (including structure composition, size, targeting peptides modified structure, and structure-activity) and targeted feature. Hopefully, it will have significant clinical implications in early diagnosis and prognosis of GBM and individual treatment.

脑胶质瘤为最常见的原发性颅内恶性肿瘤，目前临床采用的MRI探针不易穿越血脑屏障，造成超过10%的胶质母细胞瘤和30%的星形细胞瘤在MRI增强扫描中仍无法显示强化。基于前期研究和工作积累，我们发现可利用功能多肽、吲哚菁荧光染料、单分散磁性介孔氧化硅纳米颗粒，构建适于穿越血脑屏障的兼具靶向性和荧光性的新型双模态探针。本课题将探索该探针的制备方法和技术，考察其生物相容性、肿瘤靶向显影和体内分布等特性，对揭示探针的结构、尺寸大小等结构特征与材料的靶向性之间的构效关系和规律有重要意义。这一研究对早期特异性诊断肿瘤和检测预后都将具有重大的临床意义，有望应用于指导个体化治疗。

脑胶质瘤作为最常见的原发性颅内恶性肿瘤，是造成中枢神经系统疾病死亡的主要原因之一。目前，外科手术治疗仍然是临床中治疗脑胶质瘤的主要方法，因此在术前对肿瘤的精确诊断与术中对肿瘤切除的正确指导至关重要。近年来随着精准医学的迅速发展，生物分子成像的发展更加促使了疾病的诊断与治疗的准确性。因此，本课题主要利用功能多肽、吲哚菁荧光染料，构建适于穿越血脑屏障的兼具靶向性和荧光/MR的新型双模态探针，结果表明该靶向多肽修饰的双模态探针能够穿透血脑(BBB)，并靶向定位于脑胶质瘤部位并很好地显示肿瘤边界，同时荧光成像也能够灵敏地检测到肿瘤区域。另外，探针具有结构简单，生物相容性良好等功能。该探针可达到精确诊断，精准治疗的目的，有望应用于早期靶向诊断肿瘤和检测预后，对临床用药具有重大的指导意义。