近红外二区荧光/光声双模态分子成像探针用于脑胶质瘤边界精准识别研究

The accurate identification of glioma margin is a great strategic demand. The main bottleneck of glioma is the blood brain barrier (BBB), which prevents the intracerebral delivery of almost all exogenous macromolecules. Moreover, the growth nature of glioma is heterogeneous and infiltrative, which leads to the precise resection of tumor from the surrounding healthy brain tissue being difficult during surgery. In this project, we developed an IR-1061-based nanoprobe for second window (NIR-II)　fluorescence/photoacoustic bimodal imaging of glioma. The nanoprobe was prepared by a programmed assembly strategy using IR-1061 and DSPE-mPEG-NH2. The tumor vasculature targeted cyclic [RGDyK] peptides were labeled on the nanoprobe by click chemistry. The focused ultrasound with microbubbles accelerated BBB transverse of the nanoprobe and targeted the glioma tissue. The glioma tissue and brain normal tissue could be clearly identified via DSPE-mPEG-cRGD-IR-1061-based in vivo NIR-II fluorescence and photoacoustic bimodal imaging. The highlights of this project include the preparation of the nanoprobe, the combined the bimodality imaging and the accurate identification of margin. Therefore, the project gives an important contribution for promoting the application of NIR-II fluorescence and photoacoustic bimodal nanoprobe inaccurate identification of glioma margin.

本项目面向脑胶质瘤边界精准识别的重大需求，通过程序化自组装和“点击化学”等方法构建靶向脑胶质瘤新生血管的DSPE-mPEG-cRGD-IR-1061纳米探针。前期实验表明：制备的纳米探针具有良好的稳定性和单分散性，荧光最大发射波长位于近红外二区，同时表现出良好的近红外光学吸收性能。在此基础上，我们提出脑胶质瘤的影像学边界识别新方法：采用聚焦超声联合微气泡开启血脑屏障，促进纳米探针高效跨越血脑屏障，通过cRGD多肽特异性结合脑胶质瘤细胞，借助高对比度的近红外二区荧光成像，跨尺度、高穿透深度的光声成像，实现脑胶质瘤边界的精准检测。本项目突出解决近红外二区荧光/光声双模态成像探针的可控制备、高效跨越血脑屏障靶向脑胶质瘤细胞和精准识别肿瘤边界等关键科学问题，对推动影像引导脑胶质瘤精准手术具有重要意义。

本项目面向脑胶质瘤边界精准识别的重大需求，制备了多种近红外二区纳米探针，通过在纳米颗粒表明修饰多肽得到靶向脑胶质瘤的纳米探针。在此基础上，实现了多种近红外二区纳米探针高效跨越血脑屏障，特异性结合脑胶质瘤细胞，在小鼠模型上实现人脑胶质瘤原位移植小鼠模型的近红外二区成像、脑胶质瘤影像学边界检测、成像引导精准手术。本项目突出解决近红外二区成像探针的可控制备、高效跨越血脑屏障靶向脑胶质瘤细胞和精准识别肿瘤边界等关键科学问题，对推动影像引导脑胶质瘤精准手术具有重要意义。