金属有机框架材料在肿瘤标志物筛查中的研究进展

路欣; 胡亚琳; 屈子裕; 沈丽悦; 董嘉晖; 谢洁; 彭涛

doi:10.12338/j.issn.2096-9015.2022.0287

金属有机框架材料在肿瘤标志物筛查中的研究进展

doi: 10.12338/j.issn.2096-9015.2022.0287

路欣^1,,
胡亚琳^{1, 2},
屈子裕¹,
沈丽悦^{1, 2},
董嘉晖^{1, 2},
谢洁¹,
彭涛^1, ,

1.
中国计量科学研究院，北京 100029
2.
中国计量大学，杭州 310018

基金项目: 国家重点研发计划项目(2022YFF0608402)；中央公益类科研机构基础研究经费(AKYZD2111-2)。

详细信息

作者简介:
路欣（1999-），中国计量科学研究院在读研究生，研究方向：基于纳米材料的免疫快速检测技术，邮箱：13331218159@163.com

通讯作者:
彭涛（1990-），中国计量科学研究院副研究员，研究方向：免疫检测技术与生物计量，邮箱：pengtao@nim.ac.cn

中图分类号: TB99
计量
- 文章访问数: 317
- HTML全文浏览量: 138
- PDF下载量: 35
- 被引次数: 0
出版历程
- 收稿日期: 2022-11-25
- 录用日期: 2022-12-26
- 修回日期: 2022-12-23
- 网络出版日期: 2023-07-07
- 刊出日期: 2023-04-18

Research Progress of Metal Organic Frameworks in Tumor Marker

LU Xin^1
,,
HU Yalin^{1, 2},
QU Ziyu¹,
SHEN Liyue^{1, 2},
DONG Jiahui^{1, 2},
XIE Jie¹,
PENG Tao^{1
, ,}

1.
National Institute of Metrology, Beijing 100029, China
2.
China Jiliang University, Hangzhou 310018, China

摘要

摘要: 癌症隐匿性强、发展速度快的特点，给患者疾病治疗造成极大的影响。检测癌症发生与发展中产生的肿瘤标志物对癌症早期诊断、改善预后及降低癌症死亡率具有重大的临床意义。但是，肿瘤标志物的特异度和敏感度不足，单一的肿瘤标志物检测导致误诊或漏诊的可能性增加，也无法提供对特定肿瘤类型的鉴别诊断；肿瘤标志物的检测方法较为复杂，耗时长、成本高，限制了其在临床中的应用。此外，通常人体中肿瘤标志物的含量较低、基质成分复杂，对检测技术的灵敏度和准确度提出了挑战。近年来，金属有机框架（MOFs）材料凭借其独特且优异的物理化学性能，在生物传感器的开发与肿瘤标志物的检测中得到广泛应用。简要综述了MOFs材料的结构、命名方法和功能，并对比了每类MOFs材料的固有特性、优缺点，以及在肿瘤标志物筛查中的应用研究进展，梳理总结了目前存在的问题并提出发展建议，以期为肿瘤标志物的高灵敏新型检测方法开发提供参考。
- 计量学 /
- 癌症 /
- 金属有机框架材料 /
- 肿瘤标志物 /
- 生物传感器
Abstract: Cancer's potent concealment and rapid progression significantly impact patient treatment. Detecting tumor markers produced during cancer's development is of paramount clinical importance for early diagnosis, improving prognosis, and reducing cancer mortality. However, tumor markers' specificity and sensitivity are insufficient, and single tumor marker detection increases the likelihood of misdiagnosis or missed diagnosis, hindering differential diagnosis for specific tumor types. The detection methods for tumor markers are complicated, time-consuming, and costly, limiting their clinical application. Additionally, the generally low levels of tumor markers and complex matrix composition in the human body present challenges for the sensitivity and accuracy of detection techniques. In recent years, metal-organic frameworks (MOFs) have been extensively employed in the development of biosensors and tumor marker detection due to their unique and superior physicochemical properties. This study briefly summarizes the structure, naming methods, and functions of MOFs, compares the inherent characteristics, advantages, and disadvantages of each type of MOFs, and reviews the application progress of MOFs in tumor marker screening. The existing problems and development suggestions are summarized in the hope of providing references for the development of novel, high-sensitivity detection methods for tumor markers.
- metrology /
- cancer /
- metal-organic frameworks /
- tumor markers /
- biosensors

HTML全文

图 1 基于Fe-MOFs的适配体传感器检测CEA^[30]

Figure 1. Aptasensor based on Fe-MOFs for CEA detection^[30]

下载: 全尺寸图片幻灯片

图 2 基于Zn-MOFs的电化学免疫传感器检测肺癌标志物NSE^[42]

Figure 2. Electrochemical immunosensor based on Zn-MOFs for NSE detection^[42]

下载: 全尺寸图片幻灯片

图 3 基于Zr-MOFs的电化学免疫传感器检测CEA^[46]

Figure 3. Electrochemical immunosensor based on Zr-MOFs for CEA detection^[46]

下载: 全尺寸图片幻灯片

图 4 基于La(III)-MOF的“三明治”荧光传感器检测MicroRNA-155^[60]

Figure 4. "Sandwich"-type fluorescent sensor based on La(III)-MOF for MicroRNA-155 detection^[60]

下载: 全尺寸图片幻灯片

表 1 不同金属MOFs材料对比

Table 1. Comparison of different metal MOFs materials

类别	优点	缺点	适用检测方法	检测肿瘤标志物种类
Fe-MOFs	表面易于功能化修饰、吸附封装能力强、氧化还原活性	酸碱稳定性差	电化学传感、免疫层析、适配体传感	胚胎性抗原类、糖抗原类、蛋白质类、酶类
Zn-MOFs	比表面积大、富集发光团	水不稳定、电催化性能差	电化学发光传感、光电化学传感	蛋白质类、酶类、糖抗原类
Zr-MOFs	热/化学稳定性、磷酸基团亲和性、信号放大	光催化性能差	适配体传感、电化学传感	胚胎性抗原类、糖抗原类、蛋白质类、酶类
Cu-MOFs	催化/电化学性能、孔道结构	水不稳定、热不稳定	电化学传感	胚胎性抗原类、蛋白质类
Co-MOFs	热/化学稳定性、高负载能力、活性位点多	酸不稳定、电催化性能差	电化学传感	蛋白质类、激素类、酶类
Ln-MOFs	晶体结构、光学性能出色	光致发光效率低、稳定性差	荧光、电化学发光传感	蛋白质类、胚胎性抗原类
CD-MOFs	生物相容性好、安全性高	水不稳定	电化学发光传感	蛋白质类、酶类

下载: 导出CSV

参考文献(63)

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2]	SOKOLL L J, CHAN D W. Chapter 44 - Tumor markers [M]. Academic Press, 2020: 779-793.
[3]	DUFFY M J. Tumor markers in clinical practice: A review focusing on common solid cancers [J]. Medical Principles and Practice, 2013, 22(1): 4-11.
[4]	SHI L, SHAO J, JING X, et al. Autoluminescence-Free Dual Tumor Marker Biosensing by Persistent Luminescence Nanostructures [J]. ACS Sustainable Chemistry & Engineering, 2020, 8(1): 686-694.
[5]	张亚杰, 姬爱国. 乳腺癌病理诊断中免疫组织化学检测意义分析 [J]. 系统医学, 2021, 6(23): 40-43.
[6]	JEONG S, PARK M-J, SONG W, et al. Current immunoassay methods and their applications to clinically used biomarkers of breast cancer [J]. Clinical Biochemistry, 2020, 78: 43-57.
[7]	ZONG C, WU J, WANG C, et al. Chemiluminescence Imaging Immunoassay of Multiple Tumor Markers for Cancer Screening [J]. Analytical Chemistry, 2012, 84(5): 2410-2415.
[8]	YIN S, MA Z. Electrochemical immunoassay for tumor markers based on hydrogels [J]. Expert Rev Mol Diagn, 2018, 18(5): 457-465.
[9]	LIU L, HAO Y, DENG D, et al. Nanomaterials-Based Colorimetric Immunoassays [J]. Nanomaterials (Basel), 2019, 9(3): 316-347.
[10]	TAZAWA H, SHIGEYASU K, NOMA K, et al. Tumor-targeted fluorescence labeling systems for cancer diagnosis and treatment [J]. Cancer Sci, 2022, 113(6): 1919-1929.
[11]	YAGHI O M, LI G, LI H. Selective binding and removal of guests in a microporous metal–organic framework [J]. Nature, 1995, 378(6558): 703-706.
[12]	JAMES S L. Metal-organic frameworks [J]. Chem Soc Rev, 2003, 32(5): 276-288.
[13]	孟格. 过渡金属基纳米材料的设计合成及其在能源储存和转化中的应用 [D]. 北京: 北京化工大学, 2018.
[14]	李建惠, 兰天昊, 陈杨, 等. MOF复合材料在气体吸附分离中的研究进展 [J]. 化工学报, 2021, 72(1): 167-179.
[15]	刘震震. 金属有机骨架(Cu-MOF)催化NH_3-SCR反应去除NO的研究 [D]. 大连: 大连理工大学, 2016.
[16]	汪碧如. MOF纳米复合材料的制备及其在电化学发光生物传感中的应用 [D]. 武汉: 华中农业大学, 2018.
[17]	沈宏. 核壳型MOF用于细胞内pH和酶的逐步响应成像 [D]. 南京: 南京大学, 2018.
[18]	陈玉平, 武鹤松, 陆欢, 等. 家蚕丝素蛋白诱导金属-有机骨架材料(MOF)构建核-壳结构的pH响应性抗癌药物载体[C]. 镇江: 中国蚕学会第十届青年学术研讨会, 2019.
[19]	FURUKAWA H, CORDOVA K E, O'KEEFFE M, et al. The chemistry and applications of metal-organic frameworks [J]. Science, 2013, 341(6149): 1230444.
[20]	WANG Y, YAN J, WEN N, et al. Metal-organic frameworks for stimuli-responsive drug delivery [J]. Biomaterials, 2020, 230: 119619.
[21]	韩蕊. 铁基MOFs复合材料在化学发光适配体传感器中的应用 [D]. 济南: 济南大学, 2021.
[22]	GHANBARI T, ABNISA F, WAN DAUD W M A. A review on production of metal organic frameworks (MOF) for CO2 adsorption [J]. Science of The Total Environment, 2020, 707: 135090.
[23]	EVANS J D, GARAI B, REINSCH H, et al. Metal–organic frameworks in Germany: From synthesis to function [J]. Coordination Chemistry Reviews, 2019, 380: 378-418.
[24]	BHARDWAJ N, BHARDWAJ S K, MEHTA J, et al. MOF-Bacteriophage Biosensor for Highly Sensitive and Specific Detection of Staphylococcus aureus [J]. ACS Appl Mater Interfaces, 2017, 9(39): 33589-33598.
[25]	程绍娟. 金属有机骨架配合物MOF-5的合成及其储氢性能研究 [D]. 太原: 太原理工大学, 2007.
[26]	许兰兰, 王松, 刘玉霞, 等. 微波法合成金属-有机骨架材料研究应用进展 [J]. 化工新型材料, 2019, 47(4): 1-5.
[27]	WEN T, QUAN G, NIU B, et al. Versatile Nanoscale Metal-Organic Frameworks (nMOFs): An Emerging 3D Nanoplatform for Drug Delivery and Therapeutic Applications [J]. Small, 2021, 17(8): e2005064.
[28]	WANG H S. Metal–organic frameworks for biosensing and bioimaging applications [J]. Coordination Chemistry Reviews, 2017, 349: 139-155.
[29]	JOSEPH J, IFTEKHAR S, SRIVASTAVA V, et al. Iron-based metal-organic framework: Synthesis, structure and current technologies for water reclamation with deep insight into framework integrity [J]. Chemosphere, 2021, 284: 131171.
[30]	LI J, LIU L, AI Y, et al. Self-Polymerized Dopamine-Decorated Au NPs and Coordinated with Fe-MOF as a Dual Binding Sites and Dual Signal-Amplifying Electrochemical Aptasensor for the Detection of CEA [J]. ACS Applied Materials & Interfaces, 2020, 12(5): 5500-5510.
[31]	CHEN R, CHEN X, ZHOU Y, et al. "Three-in-One" Multifunctional Nanohybrids with Colorimetric Magnetic Catalytic Activities to Enhance Immunochromatographic Diagnosis [J]. ACS Nano, 2022, 16(2): 3351-3361.
[32]	SHU Y, YE Q, DAI T, et al. Encapsulation of Luminescent Guests to Construct Luminescent Metal–Organic Frameworks for Chemical Sensing [J]. ACS Sensors, 2021, 6(3): 641-658.
[33]	ZHANG X, LI G, WU D, et al. Recent progress in the design fabrication of metal-organic frameworks-based nanozymes and their applications to sensing and cancer therapy [J]. Biosensors and Bioelectronics, 2019, 137: 178-198.
[34]	LI X, LI X, LI D, et al. Electrochemical biosensor for ultrasensitive exosomal miRNA analysis by cascade primer exchange reaction and MOF@Pt@MOF nanozyme [J]. Biosensors and Bioelectronics, 2020, 168: 112554.
[35]	WANG Z, JIANG X, YUAN R, et al. N-(aminobutyl)-N-(ethylisoluminol) functionalized Fe-based metal-organic frameworks with intrinsic mimic peroxidase activity for sensitive electrochemiluminescence mucin1 determination [J]. Biosensors and Bioelectronics, 2018, 121: 250-256.
[36]	LI C, LI Y, ZHANG Y, et al. Signal-enhanced electrochemiluminescence strategy using iron-based metal-organic frameworks modified with carboxylated Ru(II) complexes for neuron-specific enolase detection [J]. Biosensors and Bioelectronics, 2022, 215: 114605.
[37]	WANG M, HU M, LI Z, et al. Construction of Tb-MOF-on-Fe-MOF conjugate as a novel platform for ultrasensitive detection of carbohydrate antigen 125 and living cancer cells [J]. Biosensors and Bioelectronics, 2019, 142: 111536.
[38]	LI H, EDDAOUDI M, O'KEEFFE M, et al. Design and synthesis of an exceptionally stable and highly porous metal-organic framework [J]. Nature, 1999, 402(6759): 276-279.
[39]	ZHOU N, SU F, GUO C, et al. Two-dimensional oriented growth of Zn-MOF-on-Zr-MOF architecture: A highly sensitive and selective platform for detecting cancer markers [J]. Biosensors and Bioelectronics, 2019, 123: 51-58.
[40]	BAHARI D, BABAMIRI B, MORADI K, et al. Graphdiyne nanosheet as a novel sensing platform for self-enhanced electrochemiluminescence of MOF enriched ruthenium (II) in the presence of dual co-reactants for detection of tumor marker [J]. Biosensors and Bioelectronics, 2022, 195: 113657.
[41]	MO G, HE X, QIN D, et al. A potential-resolved electrochemiluminescence resonance energy transfer strategy for the simultaneous detection of neuron-specific enolase and the cytokeratin 19 fragment [J]. Analyst, 2021, 146(4): 1334-1339.
[42]	MA E, WANG P, YANG Q, et al. Electrochemical Immunosensors for Sensitive Detection of Neuron-Specific Enolase Based on Small-Size Trimetallic Au@Pd^Pt Nanocubes Functionalized on Ultrathin MnO(2) Nanosheets as Signal Labels [J]. ACS Biomater Sci Eng, 2020, 6(3): 1418-1427.
[43]	WEI Q, WANG C, ZHOU X, et al. Ionic liquid and spatially confined gold nanoparticles enhanced photoelectrochemical response of zinc-metal organic frameworks and immunosensing squamous cell carcinoma antigen [J]. Biosensors and Bioelectronics, 2019, 142: 111540.
[44]	CAVKA J H, JAKOBSEN S, OLSBYE U, et al. A New Zirconium Inorganic Building Brick Forming Metal Organic Frameworks with Exceptional Stability [J]. Journal of the American Chemical Society, 2008, 130(42): 13850-13851.
[45]	韩易潼, 刘民, 李克艳, 等. 高稳定性金属有机骨架UiO-66的合成与应用 [J]. 应用化学, 2016, 33(4): 367-378.
[46]	BAO T, FU R, WEN W, et al. Target-Driven Cascade-Amplified Release of Loads from DNA-Gated Metal–Organic Frameworks for Electrochemical Detection of Cancer Biomarker [J]. ACS Applied Materials & Interfaces, 2020, 12(2): 2087-2094.
[47]	XIONG X, ZHANG Y, WANG Y, et al. One-step electrochemiluminescence immunoassay for breast cancer biomarker CA 15-3 based on Ru(bpy)62+-coated UiO-66-NH2 metal-organic framework [J]. Sensors and Actuators B: Chemical, 2019, 297: 126812.
[48]	WU Y, HAN J, XUE P, et al. Nano metal–organic framework (NMOF)-based strategies for multiplexed microRNA detection in solution and living cancer cells [J]. Nanoscale, 2015, 7(5): 1753-1759.
[49]	WEI Y P, ZHANG Y W, MAO C J. A silver nanoparticle-assisted signal amplification electrochemiluminescence biosensor for highly sensitive detection of mucin 1 [J]. J Mater Chem B, 2020, 8(12): 2471-2475.
[50]	HUANG X, HE Z, GUO D, et al. "Three-in-one" Nanohybrids as Synergistic Nanoquenchers to Enhance No-Wash Fluorescence Biosensors for Ratiometric Detection of Cancer Biomarkers [J]. Theranostics, 2018, 8(13): 3461-3473.
[51]	BANERJEE A, SINGH U, ARAVINDAN V, et al. Synthesis of CuO nanostructures from Cu-based metal organic framework (MOF-199) for application as anode for Li-ion batteries [J]. Nano Energy, 2013, 2(6): 1158-1163.
[52]	HATAMI Z, JALALI F, AMOUZADEH TABRIZI M, et al. Application of metal-organic framework as redox probe in an electrochemical aptasensor for sensitive detection of MUC1 [J]. Biosensors and Bioelectronics, 2019, 141: 111433.
[53]	ZHOU L, YANG L, WANG C, et al. Copper doped terbium metal organic framework as emitter for sensitive electrochemiluminescence detection of CYFRA 21-1 [J]. Talanta, 2022, 238: 123047.
[54]	XIE J, CHENG D, LI P, et al. Au/Metal–Organic Framework Nanocapsules for Electrochemical Determination of Glutathione [J]. ACS Applied Nano Materials, 2021, 4(5): 4853-4862.
[55]	HAN W, HUANG X, LU G, et al. Research Progresses in the Preparation of Co-based Catalyst Derived from Co-MOFs and Application in the Catalytic Oxidation Reaction [J]. Catalysis Surveys from Asia, 2019, 23(2): 64-89.
[56]	DAI L, LI Y, WANG Y, et al. A prostate-specific antigen electrochemical immunosensor based on Pd NPs functionalized electroactive Co-MOF signal amplification strategy [J]. Biosensors and Bioelectronics, 2019, 132: 97-104.
[57]	XU W, QIN Z, HAO Y, et al. A signal-decreased electrochemical immunosensor for the sensitive detection of LAG-3 protein based on a hollow nanobox-MOFs/AuPt alloy [J]. Biosensors and Bioelectronics, 2018, 113: 148-156.
[58]	ZHANG Y, LI N, XU Y, et al. An ultrasensitive dual-signal aptasensor based on functionalized Sb@ZIF-67 nanocomposites for simultaneously detect multiple biomarkers [J]. Biosensors and Bioelectronics, 2022, 214: 114508.
[59]	WANG S, ZHAO Y, WANG M, et al. Enhancing Luminol Electrochemiluminescence by Combined Use of Cobalt-Based Metal Organic Frameworks and Silver Nanoparticles and Its Application in Ultrasensitive Detection of Cardiac Troponin I [J]. Analytical Chemistry, 2019, 91(4): 3048-3054.
[60]	AFZALINIA A, MIRZAEE M. Ultrasensitive Fluorescent miRNA Biosensor Based on a "Sandwich" Oligonucleotide Hybridization and Fluorescence Resonance Energy Transfer Process Using an Ln(III)-MOF and Ag Nanoparticles for Early Cancer Diagnosis: Application of Central Composite Design [J]. ACS Appl Mater Interfaces, 2020, 12(14): 16076-16087.
[61]	陆洪军, 杨小宁, 沙靖全, 等. β-环糊精金属有机骨架材料的合成及对阿奇霉素的包合研究 [J]. 哈尔滨理工大学学报, 2015, 20(4): 35-40.
[62]	WANG Y, LI Y, ZHUANG X, et al. Ru(bpy)32+ encapsulated cyclodextrin based metal organic framework with improved biocompatibility for sensitive electrochemiluminescence detection of CYFRA21-1 in cell [J]. Biosensors and Bioelectronics, 2021, 190: 113371.
[63]	MA H, LI X, YAN T, et al. Electrochemiluminescent immunosensing of prostate-specific antigen based on silver nanoparticles-doped Pb (II) metal-organic framework [J]. Biosensors and Bioelectronics, 2016, 79: 379-385.