Key Laboratory for Advanced Materials & Feringa Nobel Prize Scientist Joint Research Center, East China University of Science and Technology (ECUST), 130 Meilong Rd., Shanghai 200237, PR China.
International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, the Second Military Medical University, Shanghai 200433, PR China.
Theranostics. 2018 May 11;8(12):3268-3274. doi: 10.7150/thno.24711. eCollection 2018.
The ability of chemical tools to effectively detect malignancy in frozen sections removed from patients during surgery is important for the timely determination of the subsequent surgical program. However, current clinical methods for tissue imaging rely on dye-based staining or antibody-based techniques, which are sluggish and complicated. Here, we have developed a 2D material-based supramolecular imaging probe for the simple, rapid yet precise diagnosis of hepatocellular carcinoma (HCC). The 2D probe is constructed through supramolecular self-assembly between a water soluble, fluorescent peptide ligand that selectively targets glypican-3 (GPC-3, a specific cell-surface biomarker for HCC) and 2D molybdenum disulfide that acts as a fluorescence quencher as well as imaging enhancer. We show that the 2D imaging probe developed with minimal background fluorescence can sensitively and selectively image cells overexpressing GPC-3 over a range of control cells expressing other membrane proteins. Importantly, we demonstrate that the 2D probe is capable of rapidly (signal became readable within 1 min) imaging HCC tissues over para-carcinoma regions in frozen sections derived from HCC patients; the results are in accordance with those obtained using traditional clinical staining methods. Compared to conventional staining methods, which are laborious (e.g., over 30 min is needed for antibody-based immunosorbent assays) and complex (e.g., diagnosis is based on discrimination of the nucleus morphology of cancer cells from that of normal cells), our probe, with its simplicity and quickness, might become a promising candidate for tumor-section staining as well as fluorescence imaging-guided surgery.
化学工具能够有效地检测手术中从患者身上切除的冷冻切片中的恶性肿瘤，这对于及时确定后续的手术方案非常重要。然而，目前用于组织成像的临床方法依赖于基于染料的染色或基于抗体的技术，这些方法既缓慢又复杂。在这里，我们开发了一种基于 2D 材料的超分子成像探针，用于简单、快速且精确地诊断肝细胞癌（HCC）。该 2D 探针通过水溶性荧光肽配体与 2D 二硫化钼之间的超分子自组装构建而成，该配体特异性靶向磷脂酰聚糖-3（GPC-3，HCC 的特定细胞表面标志物），而 2D 二硫化钼则充当荧光猝灭剂和成像增强剂。我们表明，该 2D 成像探针具有最小的背景荧光，可以敏感且选择性地对过表达 GPC-3 的细胞进行成像，而对表达其他膜蛋白的对照细胞则没有。重要的是，我们证明该 2D 探针能够快速（在 1 分钟内即可读取信号）对源自 HCC 患者的冷冻切片中的 HCC 组织进行成像，而这些结果与使用传统临床染色方法获得的结果一致。与传统的染色方法相比，该方法繁琐（例如，基于抗体的免疫吸附测定法需要 30 多分钟）且复杂（例如，诊断基于癌细胞的细胞核形态与正常细胞的细胞核形态的区分），我们的探针具有简单、快速的特点，可能成为肿瘤切片染色以及荧光成像引导手术的有前途的候选方法。
