您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

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

PDF (PC)

147

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
[1] Xu M, Jung X, Hines O J, et al. Obesity and pancreatic cancer: overview of epidemiology and potential prevention by weight loss [J]. Pancreas, 2018, 47(2): 158-162.
[2] Gajiwala S, Torgeson A, Garrido-Laguna I, et al. Combination immunotherapy and radiation therapy strategies for pancreatic cancer-targeting multiple steps in the cancer immunity cycle [J]. J Gastrointest Oncol, 2018, 9(6): 1014-1026.
[3] Saravanakumar K, Hu X, Ali D M, et al. Emerging strategies in stimuli-responsive nanocarriers as the drug delivery system for enhanced cancer therapy [J]. Curr Pharm Des, 2019, 25(24): 2609-2625.
[4] Xu T, Ding W, Ji X, et al. Molecular mechanisms of ferroptosis and its role in cancer therapy [J]. J Cell Mol Med, 2019, 23(8): 4900-4912.
[5] Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death [J]. Cell, 2012, 149(5): 1060-1072.
[6] Shen Z, Song J, Yung BC, et al. Emerging strategies of cancer therapy based on ferroptosis [J]. Adv Mater, 2018, 30(12): e1704007.doi:10.1002/adma.201704007
[7] Morris JT, Wang SC, Hebrok M. KRAS, Hedgehog, Wnt and the twisted developmental biology of pancreatic ductal adenocarcinoma [J]. Nat Rev Cancer, 2010, 10(10): 683-695.
[8] Ansari D, Carvajo M, Bauden M, et al. Pancreatic cancer stroma: controversies and current insights [J]. Scand J Gastroenterol, 2017, 52(6-7): 641-646.
[9] Stathis A, Moore MJ. Advanced pancreatic carcinoma: current treatment and future challenges [J]. Nat Rev Clin Oncol, 2010, 7(3): 163-172.
[10] Arlt A, Muerkoster SS, Schafer H. Targeting apoptosis pathways in pancreatic cancer [J]. Cancer Lett, 2013, 332(2): 346-358.
[11] Wolske KM, Ponnatapura J, Kolokythas O, et al. Chronic pancreatitis or pancreatic tumor? A problem-solving approach [J]. Radiographics, 2019, 39(7): 1965-1982.
[12] Feng W, Han X, Wang R, et al. Nanocatalysts-augmented and photothermal-enhanced tumor-specific sequential nanocatalytic therapy in both NIR-I and NIR-II biowindows [J]. Adv Mater, 2019, 31(5): e1805919. doi:10.1002/adma.201805919
[13] Gao M, Yi J, Zhu J, et al. Role of Mitochondria in Ferroptosis [J]. Mol Cell, 2019, 73(2): 354-363.
[14] Zheng DW, Lei Q, Zhu JY, et al. Switching apoptosis to ferroptosis: metal-organic network for high-efficiency anticancer therapy [J]. Nano Lett, 2017, 17(1): 284-291.
[15] Sabharwal SS, Schumacker PT. Mitochondrial ROS in cancer: initiators, amplifiers or an Achilles heel? [J]. Nat Rev Cancer, 2014, 14(11): 709-721.
[16] Baulies A, Montero J, Matias N, et al. The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading [J]. Redox Biol, 2018, 14(1): 164-177.
[17] Gong N, Ma X, Ye X, et al. Carbon-dot-supported atomically dispersed gold as a mitochondrial oxidative stress amplifier for cancer treatment [J]. Nat Nanotechnol, 2019, 14(4): 379-387.
[18] Yang B, Liu Q, Yao X, et al. FePt@MnO-Based Nanotheranostic platform with acidity-triggered dual-Ions release for enhanced MR imaging-guided ferroptosis chemodynamic terapy [J]. ACS Appl Mater Interfaces, 2019, 11(42): 38395-38404.
[19] Shen Z, Liu T, Li Y, et al. Fenton-reaction-acceleratable magnetic nanoparticles for ferroptosis therapy of prthotopic brain tumors [J]. ACS Nano, 2018, 12(11): 11355-11365.
[20] Bebber CM, Muller F, Prieto CL, et al. Ferroptosis in cancer cell biology [J]. Cancers(Basel), 2020, 12(1): 164.
[21] Xiang Y, Li N, Guo L, et al. Biocompatible and pH-sensitive MnO-loaded carbonaceous nanospheres(MnO@CNSs): a theranostic agent for magnetic resonance imaging-guided photothermal therapy [J]. Carbon, 2018, 136(1): 113-124.
[22] Qi Y, Li W, Fang J, et al. Application and mechanism of manganese-coated caramelization nanospheres for active targeting in hepatobiliary tumors [J]. Nanomedicine(Lond), 2019, 14(22): 2973-2985.
[23] Silambarasu A, Manikandan A, Balakrishnan K, et al. Comparative Study of Structural, Morphological, Magneto-Optical and Photo-Catalytic Properties of Magnetically Reusable Spinel MnFe2O4 Nano-Catalysts[J]. J Nanosci Nanotechnol, 2018, 18(5): 3523-3531.
[24] Huang G, Li H, Chen J, et al. Tunable T1 and T2 contrast abilities of manganese-engineered iron oxide nanoparticles through size control [J]. Nanoscale, 2014, 6(17): 10404-10412.
[25] 陶旭锋,Vay Liang W. Bill Go,肖桂山. 活性氧介导的肿瘤微环境在胰腺癌发生与发展中作用的研究进展[J]. 生理学报, 2021(11): 1-22. TAO Xufeng, Vay Liang W. Bill Go, XIAO Guishan. Rogress on the role of reactive oxygen species-mediated tumor microenvironment in pancreatic cancer [J]. Acta Physiologica Sinica, 2021(11): 1-22.
[26] Bao W, Liu X, Lv Y, et al. Nanolongan with multiple on-demand conversions for ferroptosis-apoptosis combined anticancer therapy [J]. ACS Nano, 2019, 13(1): 260-273.
[1] 姜卉,魏甜,李建平,王聪. 葛根素对索拉非尼心肌毒性的保护及作用机制[J]. 山东大学学报 (医学版), 2022, 60(8): 14-22.
[2] 陶国伟,王芳,董向毅,徐亚瑄,赵琳丽,胡蓓蓓. 子宫腺肌病的超声与MRI诊断及进展[J]. 山东大学学报 (医学版), 2022, 60(7): 56-65.
[3] 左立平,蒋丰洋,周斌彬,范金蕾,梁永锋,邓展昊,于德新. 术前MRI在预测169例肝细胞肝癌微血管侵犯及早期复发的价值[J]. 山东大学学报 (医学版), 2022, 60(3): 89-95.
[4] 冯宝民,王舟,徐晗,李佳存,于乔文,修建军. 抗髓鞘少突胶质细胞糖蛋白IgG抗体相关疾病临床及影像特征[J]. 山东大学学报 (医学版), 2022, 60(3): 45-50.
[5] 苑宝文,王沛,黄蔚. 组蛋白去乙酰化酶SIRT1对胰腺癌代谢的调控作用[J]. 山东大学学报 (医学版), 2022, 60(3): 1-12.
[6] 李雁儒,李娟,李培龙,杜鲁涛,王传新. 胰腺癌不同进展期血清外泌体蛋白质组学分析[J]. 山东大学学报 (医学版), 2022, 60(10): 33-41.
[7] 刘学业,李齐明,唐弘毅,徐秋平,陈文倩,郭泾. 年轻成人颞下颌关节髁突体积、表面积与关节盘矢向位置的关系[J]. 山东大学学报 (医学版), 2021, 59(6): 117-121.
[8] 宋珍珍,孙小玲,李海鸥,王芳,张冉,于德新. 120例胶质瘤及瘤周水肿MRI影像组学在评估肿瘤复发中的价值[J]. 山东大学学报 (医学版), 2021, 59(11): 53-60.
[9] 陈晓丽,桂振朝,高杨,邢梦瑶,修建军. 13例涎腺导管癌的影像学表现分析[J]. 山东大学学报 (医学版), 2021, 59(1): 78-82.
[10] 孙珊珊,房雷,赵翠萍,钟庆,高翔,李玲. 伴可逆性后部脑病综合征MR表现的急性间歇性卟啉病1例报告并文献复习[J]. 山东大学学报 (医学版), 2020, 58(2): 118-121.
[11] 陆菁菁,夏宇. 子宫内膜异位症的影像学诊断[J]. 山东大学学报 (医学版), 2019, 57(6): 40-45.
[12] 张晓倩,孟祥水,任庆国,南晓敏,安盼盼,帅欣艳,夏晓娜,王璇. 磁共振波谱成像对检测非痴呆型血管性认知障碍的探讨[J]. 山东大学学报 (医学版), 2019, 57(4): 42-46.
[13] 张丽红,王林省,陈东风,陈月芹,李娴,刘艳杰,李磊. 肾脏混合性上皮间质瘤的CT和MRI表现[J]. 山东大学学报 (医学版), 2018, 56(7): 70-75.
[14] 张丽红,李娴,王林省,李宏磊,李磊. 含脂肪节细胞神经瘤的影像学表现与病理对照[J]. 山东大学学报 (医学版), 2018, 56(12): 73-78.
[15] 王玉红,张丽红,王林省,陈月芹,王彦辉,王皆欢,李传福. 消化道颗粒细胞瘤的影像学表现[J]. 山东大学学报（医学版）, 2017, 55(8): 66-70.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 郑敏,郝跃伟,刘雪平,赵婷婷. 血小板膜糖蛋白Ibα基因HPA-2、Kozak序列多态性与脑梗死的相关性研究[J]. 山东大学学报(医学版), 2008, 46(3): 292 -295 .
[2] 张杰,李振华,孙晋浩,暴丽华,刘岳鹏. 恒定磁场对Schwann细胞氧化损伤的保护作用[J]. 山东大学学报(医学版), 2007, 45(3): 229 -232 .
[3] 方英立,马玉燕,刘锡梅,周文 . 急诊剖宫产患者围手术期替硝唑合理应用[J]. 山东大学学报(医学版), 2007, 45(10): 995 .
[4] 姜红菊,李润智,王营,徐冬梅,张梅,张运,李继福 . 冠状动脉粥样硬化斑块形态及介入治疗与MMP-9的关系[J]. 山东大学学报(医学版), 2008, 46(10): 966 -970 .
[5] 王术芹,齐 峰,吴剑波,孙宝柱. 罗哌卡因对大鼠离体主动脉收缩作用的钙离子调节机制[J]. 山东大学学报(医学版), 2008, 46(8): 773 -776 .
[6] 滕学仁,赵永生,胡光亮,周伦,李建民 . 两种方法保存同种异体髌腱移植重建膝关节交叉韧带的光镜电镜观察[J]. 山东大学学报(医学版), 2008, 46(10): 945 -950 .
[7] 袁吴敏,赵志伦,王洁贞 . 吸烟和饮酒与颅内肿瘤关系的Meta分析[J]. 山东大学学报(医学版), 2006, 44(11): 1146 -1149 .
[8] 李明霞,王学禹 . 儿童急性播散性脑脊髓炎31例临床与MRI特点[J]. 山东大学学报(医学版), 2008, 46(8): 828 -830 .
[9] . Graves病131治疗后1年内早发甲减影响因素分析[J]. 山东大学学报(医学版), 2009, 47(9): 5 -6 .
[10] 牛瑞,刘波,邵明举,王伟 . 非小细胞肺癌区域淋巴结中肺组织特异性基因的表达与预后的关系[J]. 山东大学学报(医学版), 2007, 45(9): 884 -885 .
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发