Hubei Key Laboratory for Precision Synthesis of Small Molecule Pharmaceuticals & Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University, Wuhan 430062, P. R. China.
Anal Chem. 2024 Nov 26;96(47):18898-18906. doi: 10.1021/acs.analchem.4c05202. Epub 2024 Nov 14.
Hepatocellular carcinoma (HCC) is a formidable disease, distinguished by its high aggressiveness and dismal outcomes. Although leucine aminopeptidase (LAP) has been widely employed as a biomarker in biological imaging of HCC, it is still susceptible to interference from false-positive signals activated in injured liver tissues. In this study, based on the significant difference of GSH levels in alcohol-damaged liver tissues and tumor tissues, a dual-tandem activatable probe (PCLT) was designed for differential diagnosis and treatment guidance of HCC by near-infrared fluorescence (NIRF) imaging. This probe comprised a dual-locked hemicyanine dye decorated with a tetraethylene glycol chain and dual-recognition unit of glutathione (GSH) and LAP, which could be sequentially cleaved by GSH and LAP to restore its NIRF signal. PCLT excellently discriminated orthotopic HCC from ALI far earlier (7 days) than histological analysis (28 days) and exhibited higher specificity toward early orthotopic HCC than the single-locked probe (PCL). In addition, PCLT is capable of accurately delineating the tumor contour, assisting in surgical resection of HCC tumors under fluorescence visualization, and noninvasively assessing the antitumor effect of HCC chemotherapy during ferroptosis, thereby presenting promising clinical implications for clinical diagnosis and therapy of HCC.
肝细胞癌（HCC）是一种侵袭性很强且预后较差的疾病。亮氨酸氨基肽酶（LAP）已被广泛用于 HCC 的生物成像中的生物标志物，但它仍容易受到损伤的肝组织中激活的假阳性信号的干扰。在这项研究中，基于酒精损伤的肝组织和肿瘤组织中谷胱甘肽（GSH）水平的显著差异，设计了一种双串联激活探针（PCLT），通过近红外荧光（NIRF）成像用于 HCC 的诊断和治疗指导。该探针由一个带有四乙二醇链的双锁定半花青染料和谷胱甘肽（GSH）和 LAP 的双识别单元组成，可依次被 GSH 和 LAP 切割以恢复其 NIRF 信号。PCLT 比组织学分析（28 天）更早（7 天）极好地区分了原位 HCC 和 ALI，并且比单锁定探针（PCL）对早期原位 HCC 具有更高的特异性。此外，PCLT 能够准确描绘肿瘤轮廓，在荧光可视化下协助 HCC 肿瘤的手术切除，并在铁死亡期间非侵入性地评估 HCC 化疗的抗肿瘤效果，因此为 HCC 的临床诊断和治疗提供了有希望的临床意义。
