Gao Min, Lee Sun Hyeok, Kwon Haw-Young, Ciaramicoli Larissa Miasiro, Jo Eunsol, Yu Young Hyun, Li Fengming, Kim Beomsue, Hong Kyungtae, Lee Jun-Seok, Kim Namhui, Oh Yoojin, Im Chun Young, Tan Chris Soon Heng, Ha Hyung-Ho, Chang Young-Tae
School of Chemistry and Chemical Engineering, Linyi University, Linyi 276005, P. R. China.
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
ACS Cent Sci. 2024 Dec 16;11(1):76-83. doi: 10.1021/acscentsci.4c01822. eCollection 2025 Jan 22.
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, and , 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 through a systematic transporter screen using a CRISPR activation library. SMPD1 was identified as the target of 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.
肝细胞癌（HCC）是目前最主要的恶性肝癌，其发病率和死亡率都很高。早期诊断和手术切除对于提高HCC患者的生存率至关重要。然而，受临床诊断方法的限制，在癌症早期很难准确区分肿瘤组织及其边界。在此，我们报告了两种荧光探针，分别用于检测癌细胞和健康细胞，通过提供互补成像实现肝癌的精确诊断。这两种荧光探针能够在肝组织成像中选择性地标记靶细胞，这一点通过苏木精-伊红（H&E）染色和抗体染色得到了证实。此外，首次通过这两种探针的组合清晰地识别出癌区和健康区，表明其在荧光引导手术中具有应用潜力。最后，我们通过使用CRISPR激活文库进行系统的转运体筛选，确定转运体SLC27A2是[探针名称1]的门控靶点。通过热蛋白质组分析确定鞘磷脂磷酸二酯酶1（SMPD1）是[探针名称2]的靶点。因此，这两种高特异性探针的开发提供了互补成像，并为癌症疾病，甚至荧光引导手术提供了一种独特的诊断工具。
