A Pair of Fluorescent Probes Enabling Precise Diagnosis of Liver Cancer by Complementary Imaging.

IF 12.7 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY ACS Central Science Pub Date : 2024-12-16 eCollection Date: 2025-01-22 DOI:10.1021/acscentsci.4c01822
Min Gao, Sun Hyeok Lee, Haw-Young Kwon, Larissa Miasiro Ciaramicoli, Eunsol Jo, Young Hyun Yu, Fengming Li, Beomsue Kim, Kyungtae Hong, Jun-Seok Lee, Namhui Kim, Yoojin Oh, Chun Young Im, Chris Soon Heng Tan, Hyung-Ho Ha, Young-Tae Chang
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Abstract

Hepatocellular carcinoma (HCC) is by far the predominant malignant liver cancer, with both high morbidity and mortality. Early diagnosis and surgical resections are imperative for improving the survival of HCC patients. However, limited by clinical diagnosis methods, it is difficult to accurately distinguish tumor tissue and its boundaries in the early stages of cancer. Herein, we report two fluorescent probes, cLG and hLR, for the detection of cancer and healthy cells, respectively, enabling the precise diagnosis of liver cancer by providing complementary imaging. These two fluorescent probes could selectively stain the target cells in the liver tissue imaging, which is confirmed by H&E and antibody staining. Moreover, for the first time, the cancerous area and healthy area are clearly identified by the cocktail of these two probes, suggesting its potential to be used in fluorescence-guided surgery. Finally, we identify transporter SLC27A2 as the gating target of cLG through a systematic transporter screen using a CRISPR activation library. SMPD1 was identified as the target of hLR through a thermal proteome profiling. Therefore, the development of these two highly specific probes offers complementary imaging and provides a unique diagnostic tool for cancer disease, even for fluorescence-guided surgery.

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肝细胞癌(HCC)是目前最主要的恶性肝癌,发病率和死亡率都很高。早期诊断和手术切除是提高 HCC 患者生存率的当务之急。然而,受限于临床诊断方法,在癌症早期很难准确分辨肿瘤组织及其边界。在此,我们报告了两种分别用于检测癌细胞和健康细胞的荧光探针--cLG 和 hLR,通过互补成像实现肝癌的精确诊断。这两种荧光探针可选择性地染色肝组织成像中的靶细胞,这一点已通过 H&E 和抗体染色得到证实。此外,这两种探针的鸡尾酒疗法首次实现了癌症区域和健康区域的清晰识别,这表明它有望用于荧光引导手术。最后,通过使用 CRISPR 激活文库对转运体进行系统筛选,我们发现转运体 SLC27A2 是 cLG 的门控靶标。通过热蛋白质组图谱分析,我们发现 SMPD1 是 hLR 的靶标。因此,这两种高度特异性探针的开发提供了互补成像,为癌症疾病甚至荧光引导手术提供了独特的诊断工具。
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来源期刊
ACS Central Science
ACS Central Science Chemical Engineering-General Chemical Engineering
CiteScore
25.50
自引率
0.50%
发文量
194
审稿时长
10 weeks
期刊介绍: ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.
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