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山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (4): 48-55.doi: 10.6040/j.issn.1671-7554.0.2020.1752

• 基础医学 • 上一篇    下一篇

MnFe2O4@CNS纳米探针在胰腺癌诊疗一体化中的价值

张高瑞1,张玉婷2,赵雨萱3,王方青3,于德新3   

  1. 1.潍坊医学院医学影像学院, 山东 潍坊 261053;2.潍坊人民医院心内一科, 山东 潍坊 261041;3.山东大学齐鲁医院放射科, 山东 济南 250012
  • 发布日期:2021-04-30
  • 通讯作者: 于德新. E-mail:ydx0330@sina.com
  • 基金资助:
    国家自然科学基金面上项目(81771888);山东省自然科学基金(ZR2017MH006)

Value of MnFe2O4@CNS in the theragnostic of pancreatic cancer

ZHANG Gaorui1, ZHANG Yuting2, ZHAO Yuxuan3, WANG Fangqing3, YU Dexin3   

  1. 1. School of Medical Imaging, Weifang Medical University, Weifang 261053, Shandong, China;
    2. Department of Cardiology, Weifang Peoples Hospital, Weifang 261041, Shandong, China;
    3. Department of Radiology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Published:2021-04-30

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摘要： 目的 探讨诱导铁死亡及实时MR监控的MnFe2O4焦糖碳纳米探针(MnFe2O4@CNS)在胰腺癌诊疗一体化中的价值。 方法 制备MnFe2O4@CNS纳米探针,表征并测定弛豫率;CCK-8检测细胞毒性,测量芬顿(Fenton)反应催化能力并检测小鼠胰腺导管上皮肿瘤细胞(Panc02)摄取情况;评价纳米探针在Panc02细胞内MR成像能力;对细胞凋亡情况及活性氧(ROS)水平进行检测,透射电镜观察细胞形态学变化。 结果 MnFe2O4@CNS的平均粒径为183 nm,弛豫率为512.58 mmol/L·s-1。与50、100、200 mg/mL的纳米探针孵育后,Panc02与人胰腺导管上皮细胞(hTERT-HPNE)相比细胞活力具有统计学差异(P<0.05);MnFe2O4@CNS具有较高的Fenton反应催化能力,且能够被肿瘤细胞摄取;随着纳米探针浓度的提高,Panc02活性氧及细胞凋亡水平随之上升,线粒体形态显示出铁死亡的特征。细胞MR显示随着孵育时间的延长纳米探针T2成像效果逐渐增强,信号强度与对照组之间有统计学差异(P<0.05)。 结论 MnFe2O4@CNS生物相容性高,能够实现MR靶向成像并通过芬顿反应诱发细胞铁死亡,在胰腺癌诊疗一体化中具有重要的潜在价值。

关键词: 胰腺癌, 芬顿反应, 铁死亡, 磁共振成像, 诊疗一体化

Abstract: Objective To investigate the value of MnFe2O4-loaded caramelized carbonaceous nanospheres(MnFe2O4@CNS)with inducing ferroptosis and synchronous MR monitoring in the theragnostic of pancreatic cancer. Methods After MnFe2O4@CNS was prepared, the characterization and relaxivity were detected. The cytotoxicity was determined with cell counting kit-8(CCK-8)assay. The Fenton reaction catalytic activity of different concentrations of MnFe2O4@CNS were evaluated. The uptake of MnFe2O4@CNS by murine pancreatic adenocarcinoma(Panc02)cells was detected. The imaging ability of MnFe2O4@CNS in Panc02 cells was evaluated. After incubation with MnFe2O4@CNS, the levels of reactive oxygen species(ROS)and cell death of Panc02 cells were evaluated and the morphological changes were observed with transmission electron microscopy(TEM). Results The average particle size of MnFe2O4@CNS was 183nm, and the relaxivity was 512.58 mmol/L·s-1. After incubation with 50, 100 and 200 μg/mL MnFe2O4@CNS, the cell viability of the human pancreatic ductal epithelial cells(hTERT-HPNE)and Panc02 were significantly different(P<0.05). The Fenton reaction of MnFe2O4@CNS was high and MnFe2O4@CNS could be ingested by cancer cells. With higher concentration of MnFe2O4@CNS, the levels of ROS and apoptosis of Panc02 cells increased gradually, and the mitochondrial morphology of Panc02 cells showed classical characteristics of ferroptosis. The MRI of Panc02 cells showed high contrast signal effect of T2 with as incubation time increased(P<0.05). Conclusion Highly biocompatible, MnFe2O4@CNS can achieve targeted MRI and induce ferroptosis of pancreatic neoplasms, which is of great value in the theragnostic of pancreatic cancer.

Key words: Pancreatic cancer, Fenton reaction, Ferroptosis, Magnetic resonance imaging, Theragnostic

中图分类号: 

  • R445.2
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