Abstract：
Rapid tissue differentiation at the molecular level is a prerequisite for precise surgical resection, which is of special value for the treatment of malignant tumors, such as glioblastoma (GBM). Herein, a SERS-active microneedle is prepared by modifying glutathione (GSH)-responsive molecules, 5,5\'-dithiobis(2-nitrobenzoic acid) (DTNB), on the surface of Au@Ag substrates for the distinction of different GBM tissues. Since the Raman signals on the surface of the DTNB@Au@Ag microneedle can be collected by both portable and benchtop Raman spectrometers, the distribution of GSH in different tissues at centimeter scale can be displayed through Raman spectroscopy and Raman imaging, and the entire analysis process can be accomplished within 12 min. Accordingly, in vivo brain tissues of orthotopic GBM xenograft mice and ex vivo tissues of GBM patients are accurately differentiated with the microneedle, and the results are well consistent with tissue staining and postoperative pathological reports. In addition, the outline of tumor, peritumoral, and normal tissues can be indicated by the DTNB@Au@Ag microneedle for at least 56 days. Considering that the tumor tissues are quickly discriminated at the molecular level without the restriction of depth, the DTNB@Au@Ag microneedle is promising to be a powerful intraoperative diagnostic tool for surgery navigation.
摘要：
分子水平的快速组织分化是精确手术切除的先决条件，这对治疗恶性肿瘤具有特殊价值，例如胶质母细胞瘤(GBM)。在这里，通过修饰谷胱甘肽（GSH）响应分子制备SERS活性微针，5,5'-二硫代双(2-硝基苯甲酸)(DTNB),在Au@Ag基底的表面上区分不同的GBM组织。由于DTNB@Au@Ag微针表面的拉曼信号可以通过便携式和台式拉曼光谱仪收集，通过拉曼光谱和拉曼成像可以显示GSH在不同组织中厘米级的分布,整个分析过程可以在12分钟内完成。因此，用微针准确区分原位GBM异种移植小鼠的体内脑组织和GBM患者的离体组织，结果与组织染色和术后病理报告吻合良好。此外,肿瘤的轮廓，肿瘤周围,和正常组织可以通过DTNB@Au@Ag微针指示至少56天。考虑到在没有深度限制的情况下，在分子水平上快速区分肿瘤组织，DTNB@Au@Ag微针有望成为手术导航的强大术中诊断工具。
