研究动态
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工程一个对于肝癌手术切除具有高灵敏度和选择性的近红外LAP荧光探针。

Engineering a near-infrared LAP fluorescent probe with high sensitivity and selectivity for surgical resection of liver cancer.

发表日期:2023 Sep 20
作者: Renfeng Jiang, Jiayu Zeng, Qian Liu, Songjiao Li, Longwei He, Dan Cheng
来源: Cellular & Molecular Immunology

摘要:

肝细胞癌 (HCC) 是一种与高死亡率和发病率相关的癌症。为了实现精确的HCC治疗诊断,开发卓越的荧光探针至关重要。然而,现有的探针对于准确识别HCC边缘和轮廓的敏感性和特异性还不足。为了诊断HCC和在手术中识别肿瘤,迫切需要开发高灵敏度和选择性的荧光探针。肝肿瘤的进展与亮氨酸氨肽酶 (LAP) 的高表达密切相关,LAP是肝癌的生物标志物。在这里,我们合理设计了一种近红外荧光探针 NLAP,该探针专门被LAP激活。该探针对LAP表现出高灵敏度(检测限 = 6.8 mU L-1)和优越的亲和力(Km = 2.98 μM)。利用该探针,我们能够区分LAP过表达的癌细胞和正常细胞,并在术中应用它来引导肝肿瘤切除。此外,通过“原位喷洒”,我们成功地利用NLAP检测了同种异位肝肿瘤小鼠中的结肠和脾脏转移瘤的LAP,并表现出良好的性能。
Hepatocellular carcinoma (HCC) is a type of cancer associated with a high rate of mortality and morbidity. In order to achieve precise HCC theranostics, it is important to develop excellent fluorescent probes. However, the existing probes are not sensitive or specific enough to accurately identify HCC margins and contours. For diagnosing HCC and identifying tumors during surgery, it is urgent to engineer highly sensitive and selective fluorescent probes. Liver tumor progression is closely associated with leucine aminopeptidase (LAP) overexpression, a biomarker of liver cancer. Herein, we have rationally designed a NIR fluorescent probe, NLAP, which is specially activated by LAP. The probe exhibited high sensitivity (detection limit = 6.8 mU L-1) and superior affinity (Km = 2.98 μM) for LAP. With this probe, we distinguished cancer cells overexpressing LAP from normal cells and applied it intraoperatively to guide liver tumor excisions. Furthermore, NLAP was employed to successfully detect the LAP of intestinal and splenic metastatic tumors in orthotopic liver tumor mice by "in situ spraying" and good performances were demonstrated.