脑胶质瘤为常见颅内恶性肿瘤，多呈浸润性生长；而脑内功能区多，故最大程度切除肿瘤同时减少功能区破坏是胶质瘤手术成败的关键。目前胶质瘤切除多凭医生主观经验判定，准确性差，因此设计可在术中定位脑胶质瘤浸润边缘的影像探针对胶质瘤精准切除有重要的临床意义。本项目拟设计一类新颖的核壳型表面增强拉曼散射探针，通过拉曼成像技术准确识别胶质瘤浸润边缘。该探针由金纳米核心、金纳米外壳及核壳间拉曼分子层构成，核壳间电磁场的叠加效应，可显著提高探针拉曼信号的强度和稳定性。经表面修饰跨血脑屏障的靶向分子和胶质瘤细胞高表达尿激酶受体的配体，该探针跨血脑屏障后可进一步靶向胶质瘤细胞，有效提高胶质瘤浸润边缘的信噪比，有望实现胶质瘤浸润边缘的准确示踪，达到手术过程中实时引导胶质瘤精准切除的目的。本项目探针的设计思路新颖，预实验结果表明项目实施的可行性良好。

Glioma is a type of malignant brain tumor with infiltrative nature. The success of surgical resection relies on the precise location of glioma margin, which is empirically determined by the surgeons. It is highly desirable in clinic to design an imaging probe that can precisely track the infiltrative margin of glioma. In this project, a novel gold nanoprobe with core-shell structure will be developed for imaging infiltrative glioma margin with high specificity and sensitivity. This Surface-Enhanced Raman Scattering (SERS) nanoprobe will be composed of a gold nanocore, a Raman molecular layer and a gold shell. The additive effect of electromagnetic fields would significantly enhance the intensity and stability of Raman signal. The nanoprobe will be functionalized with brain- and tumor-targeted ligands, which can facilitate the penetration of the Blood-Brain Barrier (BBB) and the accumulation of the probe in the infiltrative tumor region. This novel imaging probe holds the potential for guiding precise surgical resection of glioma by illuminating the tumor margin with high SERS signal-to-noise ratio. Our preliminary data have demonstrated high potential of this novel SERS probe for illuminating the margin of orhtotopic glioma xenograft in mice.