靶向示踪脑胶质瘤浸润边缘的核壳型表面增强拉曼散射探针

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.

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。

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。我们紧扣任务书中研究目标，围绕脑胶质瘤手术导航开展研究。（1）构建了一种新型的以核壳型金纳米粒为增强基底、能够跨血脑屏障并进一步靶向胶质瘤及浸润区肿瘤细胞的表面增强拉曼探针，利用表面增强共振拉曼散射技术进行手术中引导肿瘤切除，准确定位胶质瘤及其边缘；（2）进一步拓展研究，构建了一种靶向EGFRvIII的磁共振成像/表面增强共振拉曼双模态纳米探针，通过手术前磁共振成像定位和手术中表面增强共振拉曼引导胶质瘤切除，有望解决目前临床手术过程中因病人头部移位造成的术前和术中影像配准偏差，为手术精准切除提供有力保障。本项目共发表标注有本基金号SCI收录论文11篇，影响因子均大于5，其中影响因子大于10的论文有2篇。申请中国发明专利1项。以本项目为相关研究内容，协助培养博士生1人，硕士生1人。研究达到项目预期结果。项目研究所获成果对实现胶质瘤的早期干预、提高手术预后均有重要的研究价值和临床意义。