The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Angew Chem Int Ed Engl. 2021 Feb 19;60(8):3923-3927. doi: 10.1002/anie.202014839. Epub 2021 Jan 26.
Olsalazine (Olsa) is a broad-spectrum anti-cancer agent acting as a DNA-methylation inhibitor. When conjugated to 2-cyano-6-aminobenzothiazole and a peptide substrate specific for the tumor-overexpressed enzyme furin, it can self-assemble into nanoparticles that can be detected by chemical-exchange saturation-transfer magnetic-resonance imaging (CEST MRI). We report here that these nano-assemblies can also be detected with high specificity in furin-overexpressing tumor cells by Raman spectroscopy with a distinct scattering signature and demonstrate the utility of this sensing mechanism in vitro and in vivo. Our findings suggest that Raman spectroscopy could be used for high-resolution image-guided surgery to precisely delineate tumor margins during and after resection in real-time as well as to determine microscopic tumor invasion and multifocal locoregional tumor spread, which are currently impossible to visualize with available imaging technologies, including CEST MRI.
奥沙拉嗪（Olsa）是一种广谱抗癌药物，具有 DNA 甲基化抑制剂的作用。当它与 2-氰基-6-氨基苯并噻唑和一种针对肿瘤过度表达的酶 furin 的肽底物连接时，可以自组装成纳米颗粒，这些纳米颗粒可以通过化学交换饱和转移磁共振成像（CEST MRI）检测到。我们在这里报告，这些纳米组装体也可以通过拉曼光谱以独特的散射特征在 furin 过度表达的肿瘤细胞中高度特异性地检测到，并证明了这种传感机制在体外和体内的实用性。我们的研究结果表明，拉曼光谱可用于高分辨率的图像引导手术，以在切除过程中和切除后实时精确描绘肿瘤边界，并确定目前无法通过现有成像技术（包括 CEST MRI）可视化的微小肿瘤侵袭和多灶性局部区域肿瘤扩散。
