Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, USA.
Int J Cancer. 2013 May 1;132(9):2107-17. doi: 10.1002/ijc.27903. Epub 2012 Oct 30.
This research aimed to validate the specificity of the newly developed nanobeacon for imaging the Thomsen-Friedenreich (TF) antigen, a potential biomarker of colorectal cancer. The imaging agent is comprised of a submicron-sized polystyrene nanosphere encapsulated with a Coumarin 6 dye. The surface of the nanosphere was modified with peanut agglutinin (PNA) and poly(N-vinylacetamide (PNVA) moieties. The former binds to Gal-β(1-3)GalNAc with high affinity while the latter enhances the specificity of PNA for the carbohydrates. The specificity of the nanobeacon was evaluated in human colorectal cancer cells and specimens, and the data were compared with immunohistochemical staining and flow cytometric analysis. Additionally, distribution of the nanobeacon in vivo was assessed using an "intestinal loop" mouse model. Quantitative analysis of the data indicated that approximately 2 μg of PNA were detected for each milligram of the nanobeacon. The nanobeacon specifically reported colorectal tumors by recognizing the tumor-specific antigen through the surface-immobilized PNA. Removal of TF from human colorectal cancer cells and tissues resulted in a loss of fluorescence signal, which suggests the specificity of the probe. Most importantly, the probe was not absorbed systematically in the large intestine upon topical application. As a result, no registered toxicity was associated with the probe. These data demonstrate the potential use of this novel nanobeacon for imaging the TF antigen as a biomarker for the early detection and prediction of the progression of colorectal cancer at the molecular level.
这项研究旨在验证新开发的纳米信标对 Thomsen-Friedenreich（TF）抗原成像的特异性，TF 抗原是结直肠癌的一个潜在生物标志物。该成像剂由亚微米级聚苯乙烯纳米球包裹香豆素 6 染料组成。纳米球表面用花生凝集素（PNA）和聚（N-乙烯基乙酰胺（PNVA）修饰。前者与 Gal-β(1-3)GalNAc 具有高亲和力，而后者增强了 PNA 对碳水化合物的特异性。在人结直肠癌细胞和标本中评估了纳米信标的特异性，并将数据与免疫组织化学染色和流式细胞术分析进行了比较。此外，还使用“肠环”小鼠模型评估了纳米信标的体内分布。数据分析表明，每毫克纳米信标可检测到约 2μg 的 PNA。纳米信标通过表面固定的 PNA 特异性识别肿瘤相关抗原，从而特异性报告结直肠肿瘤。从人结直肠癌细胞和组织中去除 TF 会导致荧光信号丢失，这表明探针具有特异性。最重要的是，在局部应用时，探针不会在大肠中被系统吸收。因此，探针没有与毒性相关的问题。这些数据表明，这种新型纳米信标具有作为 TF 抗原的生物标志物用于早期检测和预测结直肠癌分子水平进展的潜力。
