摘要
目的探究半乳糖靶向纳米探针Gal-OH-BDP(GOB)在近红外二区(NIR-Ⅱ)进行原位肝癌荧光成像的可行性和成像效果。方法合成NIR-Ⅱ纳米荧光探针GOB, 通过人源HepG2肝癌细胞构建BALB/c裸鼠原位肝癌模型, 将12只裸鼠采用简单随机抽样法分为2组, 每组各6只。使用GOB瘤内注射法进行NIR-Ⅱ成像的记为NIR-Ⅱ GOB组, 使用吲哚菁绿(ICG)静脉注射法并先后进行近红外一区(NIR-Ⅰ)和NIR-Ⅱ成像, 分别记为NIR-Ⅰ ICG组和NIR-Ⅱ ICG组。利用NIR-Ⅰ/Ⅱ相机进行体内成像试验。使用Image J软件对图片进行荧光图像处理, 定量计算肝癌荧光图像的肿瘤-正常组织比(TNR)和肿瘤边缘分辨率, 通过石蜡切片及苏木精-伊红染色法进行病理学验证。样本数据采用t检验和方差分析。结果通过病理学成功验证了瘤内注射后GOB在肝癌组织内的靶向积累。NIR-Ⅱ GOB组的TNR高于NIR-Ⅱ ICG组和NIR-Ⅰ ICG组(5.61±0.98比3.35±0.63比2.01±0.54, F=29.022, P<0.05)。对组成TNR的3项指标(肿瘤区域荧光、正常肝组织背景荧光和环境背景荧光)进行的亚组分析结果表明, 在肿瘤区域荧光方面, NIR-Ⅱ GOB组高于NIR-Ⅱ ICG组(228.04±5.60比207.62±14.86, t=3.149, P<0.05);在正常肝组织背景荧光方面, NIR-Ⅱ GOB组低于NIR-Ⅱ ICG组(43.22±8.68比63.47±8.88, t=-3.992, P<0.05)。通过计算跨越肿瘤边缘像素点的灰度值变化率来量化肿瘤边缘分辨率, NIR-Ⅱ GOB组高于NIR-Ⅱ ICG组和NIR-Ⅰ ICG组(170.01±30.92比98.96±23.99比36.82±10.19, F=48.882, P<0.05)。结论通过瘤内注射Gal-OH-BDP纳米荧光团在NIR-Ⅱ窗口实现优于传统ICG介导的原位肝肿瘤荧光成像。
Objective To explore the feasibility and imaging performance of galactose-targeted nanoprobe Gal-OH-BDP(GOB)for orthotopic hepatocelluar carcinoma in near infrared-Ⅱ(NIR-Ⅱ)fluo-rescence imaging.Methods NIR-Ⅱ fluorescent probe COB was synthesized,and the orthotopic hepato-cellular carcinoma model of BALB/c nude mice(Hangzhou Ziyuan Experimental Animal Technology Co.,Ltd.)was established using human HepG2 hepatoma cells(Guangzhou Huatuo Biotechnology Co.,Ltd.).A total of 12 nude mice were randomly assigned into two groups using the simple random sampling,each consisting of 6 mice.Mice injected intratumorally with GOB for NIR-Ⅱ imaging were assigned into NIR-Ⅱ GOB group(6 cases),while those receiving intravenous injections of indocyanine green(ICG)and subse-quently imaged in both near infrared-Ⅰ(NIR-Ⅰ)and NIR-Ⅱ window were assigned into NIR-Ⅰ ICG group(6 cases)and NIR-Ⅱ ICG group(6 cases),respectively.The imaging experiment in vivo was car-ried out with NIR-Ⅰ/Ⅱ optical instruments.The fluorescence images were processed by Image J software,and the tumor-to-normal tissue ratio(TNR)and resolution of images of the tumor edge were quantitatively calculated.The pathology was verified by paraffin section and hematoxylin-eosin staining.The data were analyzed by t test and analysis of variance.Results Pathological validation confirmed the targeted accumulation of GOB in liver cancer tissues post-intratumoral injection.TNR in NIR-Ⅱ GOB group was higher than that in NIR-Ⅱ ICG group and NIR-Ⅰ ICG group(5.61±0.98 vs.3.35±0.63 vs.2.01±0.54,F=29.022,P<0.05).The subgroup analysis of three indexes of TNR(tumor region fluorescence,normal liver tissue background fluorescence and environmental background fluorescence)showed that in terms of tumor region fluorescence,the NIR-Ⅱ COB group showed higher levels than the NIR-Ⅱ ICG group(228.04±5.60 vs.207.62±14.86,t=3.149,P<0.05).In the normal liver tissue background fluorescence,the NIR-Ⅱ GOB group had lower fluorescence than the NIR-Ⅱ ICG group(43
作者
刘子豪
党慧萍
闫立峰
尹大龙
Liu Zihao;Dang Huiping;Yan Lifeng;Yin Dalong(Department ofGeneral Surgery,Anhui Provincial Hospital,Anhui Medical University,Hefei 230001,China;Hefei National Laboratory for Physical Sciences at the Microscale,Department of Chemical Physics,University of Science and Technology of China,Hefei 230026,China;Department of Hepatobiliary Surgery and Centre for Leading Medicine and Advanced Technologies of IHM,the First Affiliated Hospital of University of Science and Technology of China,Hefei 230036,China)
出处
《中华实验外科杂志》
CAS
2024年第7期1479-1482,共4页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金(82172071)
安徽省重点研究与开发计划(202104b11020025)。
关键词
近红外二区
荧光成像
原位肝肿瘤
半乳糖靶向
Near infrared-Ⅱ
Fluorescence imaging
Orthotopic liver tumors
Galactose-targeting
