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使用半乳糖靶向近红外二区荧光纳米探针实现原位肝细胞癌手术切缘的精准可视化及深度成像性能

Precision Visualization of Surgical Margins and Depth Imaging Performance in Orthotopic Hepatocellular Carcinoma Using Galactose-Targeted NIR-II Fluorescence Nanoprobe.

作者信息

Liu Zihao, Zeng Taofei, Dang Huiping, He Hao, Li Jingfei, Yan Lifeng, Yin Dalong

机构信息

Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.

Hefei National Laboratory for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry and Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui 230001, China.

出版信息

Anal Chem. 2025 Aug 5;97(30):16619-16627. doi: 10.1021/acs.analchem.5c02961. Epub 2025 Jul 1.

Abstract

Accurate identification of tumor margins during liver cancer resection is crucial for improving prognosis and reducing postoperative complications. This study investigated the feasibility of using a galactose-targeted nanofluorescent probe known as Gal-OH-BDP NPs (GOB NPs), which emits in the NIR-II window, for fluorescence imaging of orthotopic hepatocellular carcinoma in animal models. In vitro imaging was performed with Intralipid emulsion and chicken breast to assess the tissue penetration depth of the GOB NPs and ICG in the NIR window. In vivo NIR-I/II imaging was conducted in orthotopic liver tumor animal models. Pathological validation confirmed that intratumoral injection of GOB NPs resulted in targeted accumulation within liver cancer tissue. Quantitative image analysis revealed that GOB NPs-mediated NIR-II imaging exhibited the highest fluorescence intensity at the tumor site and the lowest background fluorescence in the liver, thus resulting in the highest tumor-to-normal liver tissue ratio (TNR) and the highest tumor margin resolution. Additionally, GOB NPs-mediated NIR-II imaging maintained effective tumor margin visibility at a depth of 8 mm, whereas ICG-mediated NIR-I/II imaging demonstrated effective detection depths limited to 2 and 5 mm, respectively. Following intravenous injection, the GOB NPs exhibited negative staining, thus clearly delineating the tumor boundaries and achieving a high contrast between the tumor and liver tissues.

摘要

在肝癌切除术中准确识别肿瘤边界对于改善预后和减少术后并发症至关重要。本研究调查了使用一种名为Gal-OH-BDP NPs(GOB NPs)的半乳糖靶向纳米荧光探针进行动物模型原位肝细胞癌荧光成像的可行性,该探针在近红外二区窗口发射荧光。使用脂质乳剂和鸡胸肉进行体外成像,以评估GOB NPs和吲哚菁绿(ICG)在近红外窗口的组织穿透深度。在原位肝肿瘤动物模型中进行体内近红外一区/二区成像。病理验证证实,瘤内注射GOB NPs导致其在肝癌组织内靶向积聚。定量图像分析显示,GOB NPs介导的近红外二区成像在肿瘤部位表现出最高的荧光强度,在肝脏中背景荧光最低,从而产生最高的肿瘤与正常肝组织比值(TNR)和最高的肿瘤边界分辨率。此外,GOB NPs介导的近红外二区成像在8 mm深度处仍能有效显示肿瘤边界,而ICG介导的近红外一区/二区成像显示的有效检测深度分别限于2 mm和5 mm。静脉注射后,GOB NPs呈现负染色,从而清晰勾勒出肿瘤边界,并在肿瘤与肝组织之间实现高对比度。

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