State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-Tech Zone, Dalian 116024, P. R. China.
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Korea.
J Am Chem Soc. 2020 Apr 1;142(13):6381-6389. doi: 10.1021/jacs.0c01365. Epub 2020 Mar 20.
The recurrence of malignant tumors is mostly caused by incompleted surgical resection. Especially, it is difficult for surgeons to detect and accurately remove metastatic tumors by predominantly using visual examination and palpation owing to the lack of effective means to specifically distinguish the boundary range between normal and tumor tissues. Thus, the development of activated fluorescent probe with superior tumor-to-normal (T/N) tissue ratios is particularly urgent in clinics. In view of CD13/aminopeptidase N (APN) regarded as a cancer-specific biomarker, mediating with progression, invasion, and migration of malignant tumor, herein, we reported an APN-responsive fluorescent probe YH-APN and demonstrated its application to distinguish cancer cells. Through spraying manner, fluorescent superior tumor-to-normal (T/N) tissue ratios (subcutaneous transplantation tumor, 13.86; hepatic metastasis, 4.42 and 6.25; splenic metastasis, 4.99) were achieved. More importantly, we have demonstrated the ability to image metastasis tumor tissue less than 1 mm in diameter, highlighting the potential for this probe to be used as a tool in surgical resection. This research may spur the use of enzyme-activatable fluorescent probes for the progress of tumor diagnosis and image-guided surgery (IGS).
肿瘤的复发主要是由于手术切除不完全所致。由于缺乏有效手段来特异性区分正常组织和肿瘤组织之间的边界范围,因此外科医生主要依靠视觉检查和触诊来检测和准确切除转移瘤,这使得他们很难做到这一点。因此,在临床上特别需要开发具有优越肿瘤与正常组织(T/N)比值的激活荧光探针。鉴于 CD13/氨肽酶 N(APN)被认为是一种癌症特异性生物标志物,介导恶性肿瘤的进展、侵袭和迁移,在此,我们报道了一种 APN 响应型荧光探针 YH-APN,并证明了其在区分癌细胞中的应用。通过喷涂方式,实现了荧光优越的肿瘤与正常组织(T/N)比值(皮下移植瘤为 13.86;肝转移瘤为 4.42 和 6.25;脾转移瘤为 4.99)。更重要的是,我们已经证明了该探针能够对直径小于 1 毫米的转移瘤组织进行成像,突出了该探针作为手术切除工具的潜力。这项研究可能会促进酶激活荧光探针在肿瘤诊断和图像引导手术(IGS)中的应用。