Clinical big-data-based design of GLUT2-targeted carbon nanodots for accurate diagnosis of hepatocellular carcinoma. Issue 45 (11th November 2022)

• Record Type: Journal Article
• Authors: Heo, Hye Jin; Park, Yoonsang; Lee, Jung Hee; Kim, Yujin; Kim, Eun Kyoung; Kim, Ga Hyun; Yu, Yeuni; Park, So Youn; Seo, Hie Bum; Pak, Kyoungjune; Goh, Tae Sik; Park, Sehyeon; Oh, Sae-Ock; Kwon, Woosung; Kim, Yun Hak
• Is Part Of: Nanoscale. Volume 14:Issue 45(2022)
• Page Start: 17053
• Page End: 17064
• Publication Date: 2022-11-11
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d2nr04238j
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : Glucosamine-labeled carbon nanodots were developed to selectively target hepatocellular carcinoma based on genomic analysis of 339 patient samples. Abstract : Despite advances in diagnostic and therapeutic methods, the prognosis of patients with hepatocellular carcinoma (HCC) remains poor due to the delay in diagnosis. Herein, we aimed to discover a highly sensitive and specific biomarker for HCC based on genomic big data analysis and create an HCC-targeted imaging probe using carbon nanodots (CNDs) as contrast agents. In genomic analysis, we selected glucose transporter 2 (GLUT2) as a potential imaging target for HCC. We confirmed the target suitability by immunohisto-chemistry tests of 339 patient samples, where 81.1% of the patients exhibited underexpression of GLUT2, i.e., higher GLUT2 intensity in non-tumor tissues than in tumor tissues. To visualize GLUT2, we conjugated CNDs with glucosamine (GLN) as a targeting ligand to yield glucosamine-labeled CNDs (GLN-CNDs). A series of in vitro and in vivo experiments were conducted on GLUT2-modified HepG2 cells to confirm the specificity of the GLN-CNDs. Since the GLUT2 expression is higher in hepatocytes than in HCC cells, the GLUT2-targeted contrast agent is highly attached to normal cells. However, it is possible to produce images in the same form as the images obtained with a cancer cell-targeted contrast agent by inverting color scaling. Our results indicate that GLUT2 is a promising target for HCC and that GLN-CNDs may potentially be used as targeted imaging probes for diagnosing HCC.