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近红外二区小分子有机探针IR-PEG-FA在肝癌术中导航中的应用

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目的 探讨近红外二区(NIR-Ⅱ)小分子有机探针IR-PEG-FA(IPF)在肝癌术中导航的应用潜力,并进行体内近红外荧光(NIRF)成像研究和体内外生物安全性评估。方法 在课题组的研究基础上,通过化学合成方法构建一种靶向肝癌特异性生物标志物的NIR-Ⅱ小分子有机探针。用MTT法检测该纳米探针对肝癌细胞株BEL-7402、HepG-2、HuH-7及正常肝细胞HL-7702活性的影响;通过溶血实验、急性毒性实验和血生化检测对纳米探针的体内生物相容性进行评估;建立小鼠原位肝癌模型,分为IPF实验组、IP对照组、生理盐水对照组,实验组尾静脉注射IPF,对照组尾静脉分别注射IP和生理盐水,随后利用NIR-Ⅱ窗口成像技术检测其纳米探针IPF的特异肿瘤靶向性;最后在NIRF操作窗口下进行实时导航切除肝细胞肿瘤。结果 纳米探针IPF对BEL-7402、HepG-2、HuH-7及HL-7702细胞无明显毒性,溶血率均低于3%的安全限度,未引起显著红细胞损伤;急性毒性实验中小鼠无异常行为和死亡情况,且对各重要脏器(心、肝、脾、肺、肾)正常结构和功能未产生明显影响;小鼠肝功和肾功血生化指标均在正常范围内;利用IPF纳米探针进行肝肿瘤细胞标记,在NIRF窗口下观察到肝癌细胞的荧光信号,手术后切除区域的荧光信号消失。结论 NIR-Ⅱ小分子有机探针IPF具有良好的细胞安全性、优异的生物相容性,能够高效地标记肝癌细胞,具备肝癌术中导航潜力,能够为肝癌治疗的相关研究提供借鉴。
NIR-Ⅱ small molecule organic probe IR-PEG-FA for intraoperative navigation in hepatocellular carcinoma
Objective To explore the potential of IR-PEG-FA(IPF),a near-infrared two-region(NIR-Ⅱ)small-molecule organic probe,for intraoperative navigation in hepatocellular carcinoma and to perform in vivo near-infrared fluorescence(NIRF)imaging studies and ex vivo and in vivo biosafety assessments.Methods Based on the research of the group,a NIR-Ⅱ small molecule organic probe targeting specific biomarkers of hepatocellular carcinoma was constructed by chemical synthesis.The effects of the nanoprobe on the activities of hepatocellular carcinoma cell lines BEL-7402,HepG-2,HuH-7 and normal hepatocytes HL-7702 were detected by MTT assay;the in vivo biocompatibility of the nanoprobe was evaluated by haemolysis assay,acute toxicity assay and blood biochemistry assay;the in situ hepatocellular carcinoma model was established in mice,and divided into IPF experimental group,IP control group and saline control group.The experimental group was injected with IPF in the tail vein,and the control group was injected with IP and saline in the tail vein,and the specific tumour targeting of their nanoprobe IPF was subsequently detected by using NIR-Ⅱ window imaging;finally,real-time navigational resection of hepatocellular tumours was performed under the NIRF operation window.Results The nanoprobe IPF has no obvious toxicity to BEL-7402,HepG-2,HuH-7 and HL-7702 cells,and the haemolysis rate is below the safety limit of 3%,and it did not cause any significant erythrocyte damage;there is no abnormal behaviour or death of the mice in the acute toxicity test,and there is no obvious effect on the normal structure and function of the important organs(heart,liver,spleen,lungs and kidneys);the liver and kidney functions of mice are all within the normal range.Using IPF nanoprobes for liver tumour cell labelling,the fluorescent signals of hepatocellular carcinoma cells were observed under the NIRF window,and the fluorescent signals in the resected area disappeared after the surgery.Conclusion NIR-Ⅱ small molecule organic probe IPF has good cell safety,excellent biocompatibility,and can efficiently label hepatocellular carcinoma cells,possessing the potential of intraoperative navigation in hepatocellular carcinoma,which provides an idea and a reference for the research related to hepatocellular carcinoma treatment.

hepatocellular carcinomanear-infrared Ⅱ fluorescence imaginghepatectomyintraoperative navigation

徐钰叶、高琴、李科、王雅飞、程梓荷、董储瑜、王珂欣、潘奇

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西安医学院第二临床医学院,陕西 西安 710000

西安医学院第二附属医院影像科,陕西 西安 710038

西安医学院基础与转化医学研究所,陕西 西安 710021

肝细胞癌 近红外二区荧光成像 肝切除术 术中导航

陕西省科技厅重点研发项目陕西省教育厅服务地方专项西安市科技局医学研究一般项目西安医学院第二附属医院院级课题西安医学院第二附属医院院级课题西安医学院第二附属医院院级课题大学生创新创业计划训练项目大学生创新创业计划训练项目

2021SF-27122JC05624YXYJ018824KY010224KY010624KY0121S202311840014121524099

2024

分子影像学杂志
南方医科大学

分子影像学杂志

CSTPCD
ISSN:1674-4500
年,卷(期):2024.47(9)