Surface-Enhanced Resonance Raman Scattering-Guided Brain Tumor Surgery Showing Prognostic Benefit in Rat Models
Surface-Enhanced Resonance Raman Scattering-Guided Brain Tumor Surgery Showing Prognostic Benefit in Rat Models
复制标题
表面增强共振拉曼散射引导脑肿瘤手术在大鼠模型中显示出预后益处
DOI：
10.1021/acsami.9b00227
复制
发表时间：
2019-05-01
影响因子：
9.5
通讯作者：
Li, Cong
中科院分区：
文献类型：
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作者：
Han, Limei;Duan, Wenjia;Li, Cong
胶质瘤是恶性脑肿瘤中最常见的一种。手术切除是神经胶质瘤治疗的主要策略。然而，由于胶质瘤的浸润性，手术中神经外科医生很难确定胶质瘤的真实边缘。肿瘤残留或显微卫星灶残留于切除床内是导致早期复发和预后差的主要原因。在这项研究中，表面增强共振拉曼散射（SERRS）探针被开发用于术中指导胶质瘤切除术。在该探针中，在近红外波长范围内具有吸收最大值的分子报告被共价官能化在金纳米表面。该探针在水溶液中具有极高的灵敏度，检测限为5.0 pM。通过在小鼠背侧皮肤窗腔内培养异种胶质瘤，研究了该探针从肿瘤血管渗漏的外溢随时间和距离肿瘤边界的变化。重要的是，该探针具有高信号背景比，可以划定肿瘤移植物的浸润边缘。术前磁共振成像（MRI）首先明确同种异种胶质瘤在模型大鼠大脑中的位置，并设计开颅方案。在手持式拉曼扫描仪辅助下，术中逐步切除脑肿瘤，直至探头拉曼信号在切除床上完全消失。值得注意的是，纵向MRI显示，与白光引导手术相比，serrs引导手术显著降低了肿瘤复发率，提高了大鼠模型的总生存率。总的来说，这项工作在动物模型中证明了serrs引导的胶质瘤手术的预后益处。由于肿瘤浸润边缘的描绘是外科医生面临的一个共同挑战，这种具有皮摩尔检测极限的SERRS探针有望改善不同类型浸润性肿瘤的手术效果。
Glioma is the most frequent form of malignant brain tumors. Surgical debulking is a major strategy for glioma treatment. However, there is a great challenge for the neurosurgeons to intraoperatively identify the true margins of glioma because of its infiltrative nature. Tumor residues or microscopic satellite foci left in the resection bed are the main reasons leading to early recurrence as well as poor prognosis. In this study, a surface-enhanced resonance Raman scattering (SERRS) probe was developed to intraoperatively guide glioma resection. In this probe, molecular reporters with absorptive maxima at the near-infrared wavelength range were covalently functionalized on the surface of gold nanostars. This SERRS probe demonstrated an ultrahigh sensitivity with a detection limit of 5.0 pM in aqueous solution. By the development of glioma xenografts in a mouse dorsal skin window chamber, extravasation of this probe from leaky tumor vasculature as functions of time and distance to tumor boundary was investigated. Importantly, the invasive margin of the tumor xenograft was demarcated by this probe with a high signal-to-background ratio. Preoperative magnetic resonance imaging (MRI) first defined the position of orthotopic glioma xenografts in the brain of rat models, and the craniotomy plan was designed. The brain tumor was then excised intraoperatively step-by-step with the assistance of a handheld Raman scanner till the Raman signals of the probe completely disappeared in the resection bed. Notably, longitudinal MRI showed that SERRS-guided surgery significantly reduced the tumor recurrence rate and improved the overall survival of rat models compared with the white light-guided surgery. Overall, this work demonstrates the prognostic benefit of SERRS-guided glioma surgery in animal models. Because delineation of tumor-invasive margins is a common challenge faced by the surgeons, this SERRS probe with a picomolar detection limit holds the promise in improving the surgical outcome of different types of infiltrated tumors.