High Precision Imaging of Microscopic Spread of Glioblastoma with a Targeted Ultrasensitive SERRS Molecular Imaging Probe.
High Precision Imaging of Microscopic Spread of Glioblastoma with a Targeted Ultrasensitive SERRS Molecular Imaging Probe.
复制标题
使用靶向超灵敏 SERRS 分子成像探针对胶质母细胞瘤的微观扩散进行高精度成像
DOI：
10.7150/thno.13842
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发表时间：
2016
期刊：
影响因子：
12.4
通讯作者：
Kircher MF
中科院分区：
文献类型：
--
作者：
Huang R;Harmsen S;Samii JM;Karabeber H;Pitter KL;Holland EC;Kircher MF
多形性胶质母细胞瘤(GBM)等恶性脑肿瘤患者预后差的主要原因是其弥漫性生长模式和早期显微肿瘤扩散到大脑的远处。由于目前的成像方式不能显示显微肿瘤的病灶，所以仍然不可能指导最佳的治疗方法。在这里，我们探索了整合素靶向的表面增强共振拉曼光谱(SERRS)纳米颗粒在GBM小鼠模型中描述真实肿瘤范围的能力，该模型非常接近于人类的病理。最近开发的SERRS纳米颗粒具有在飞摩尔范围内的检测灵敏度。在同一小鼠中，通过拉曼多路传输直接比较了用于整合素靶向的RGD-肽结合版本(RGD-SerRS)和其非靶向RAD-SerRS对照。在注射RGD-SerRS纳米粒前用RGD多肽预封闭以验证整合素靶向的特异性。与目前认为增强的渗透性和滞留(EPR)效应导致基线摄取纳米颗粒而不考虑其表面化学成分相反，整合素靶向被证明是高度特异性的，预封闭后的蓄积明显较低。虽然非靶向SERRS颗粒能够描绘主要肿瘤，但RGD-SERRS纳米颗粒在显示主要肿瘤的真实范围和弥漫边缘方面提供了重大改进。这包括检测到远离主肿瘤的意外肿瘤区域，直径为2-3个细胞的迁移细胞的踪迹，甚至是少于5个细胞的孤立的远处肿瘤细胞群。这种基于拉曼光谱的纳米粒子成像技术有望实现对恶性脑瘤真实范围的高精度可视化。
The dismal prognosis of patients with malignant brain tumors such as glioblastoma multiforme (GBM) is attributed mostly to their diffuse growth pattern and early microscopic tumor spread to distant regions of the brain. Because the microscopic tumor foci cannot be visualized with current imaging modalities, it remains impossible to direct treatments optimally. Here we explored the ability of integrin-targeted surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles to depict the true tumor extent in a GBM mouse model that closely mimics the pathology in humans. The recently developed SERRS-nanoparticles have a sensitivity of detection in the femtomolar range. An RGD-peptide-conjugated version for integrin-targeting (RGD-SERRS) was compared directly to its non-targeted RAD-SERRS control in the same mice via Raman multiplexing. Pre-blocking with RGD peptide before injection of RGD-SERRS nanoparticles was used to verify the specificity of integrin-targeting. In contrast to the current belief that the enhanced permeability and retention (EPR) effect results in a baseline uptake of nanoparticles regardless of their surface chemistry, integrin-targeting was shown to be highly specific, with markedly lower accumulation after pre-blocking. While the non-targeted SERRS particles enabled delineation of the main tumor, the RGD-SERRS nanoparticles afforded a major improvement in visualization of the true extent and the diffuse margins of the main tumor. This included the detection of unexpected tumor areas distant to the main tumor, tracks of migrating cells of 2-3 cells in diameter, and even isolated distant tumor cell clusters of less than 5 cells. This Raman spectroscopy-based nanoparticle-imaging technology holds promise to allow high precision visualization of the true extent of malignant brain tumors.