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化学进展 2020, Vol. 32 Issue (9): 1264-1273 DOI: 10.7536/PC200108 前一篇   后一篇

• 综述 •

氧化铁纳米颗粒在磁共振成像中的应用

秦苗1,2, 徐梦洁1,2, 黄棣1,2,**(), 魏延1,2, 孟延锋3,**(), 陈维毅1,2   

  1. 1. 太原理工大学生物医学工程学院 生物医学工程系 纳米生物材料与再生医学研究中心 太原 030024
    2. 太原理工大学生物医学工程研究所 材料强度与结构冲击山西省重点实验室 太原 030024
    3. 山西医科大学附属太原市中心医院 太原 030024
  • 收稿日期:2020-01-09 修回日期:2020-02-15 出版日期:2020-09-24 发布日期:2020-06-30
  • 通讯作者: 黄棣, 孟延锋
  • 作者简介:
    **Corresponding author e-mail: (Di Huang); (Yanfeng Meng)
  • 基金资助:
    *国家自然科学基金项目(U1967215); *国家自然科学基金项目(81671789); *国家自然科学基金项目(11502158)
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Iron Oxide Nanoparticles in the Application of Magnetic Resonance Imaging

Miao Qin1,2, Mengjie Xu1,2, Di Huang1,2,**(), Yan Wei1,2, Yanfeng Meng3,**(), Weiyi Chen1,2   

  1. 1. Research Center for Nano-Biomaterials & Regenerative Medicine, Department of Biomedical Engineering, College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024, China
    2. Institute of Applied Mechanics & Biomedical Engineering, Shanxi Key Laboratory of Materials Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China
    3. The Affiliated Taiyuan Central Hospital of Shanxi Medical University, Taiyuan 030024, China
  • Received:2020-01-09 Revised:2020-02-15 Online:2020-09-24 Published:2020-06-30
  • Contact: Di Huang, Yanfeng Meng
  • Supported by:
    The work was supported by the National Natural Science Foundation of China(U1967215); The work was supported by the National Natural Science Foundation of China(81671789); The work was supported by the National Natural Science Foundation of China(11502158)

目前临床诊断中钆基造影剂的应用十分广泛,然而其对人体的毒性无法忽视,因此研究者致力于低毒性造影剂的研发。氧化铁纳米颗粒(Iron Oxide Nanoparticles,IONP)因其超顺磁性在磁共振成像(Magnetic Resonance Imaging,MRI)中具有良好的暗对比效果,并且具有良好的生物相容性。随着生物材料和分子影像技术的发展,IONP在MRI成像中的应用愈发广泛。近年来,IONP在多模态成像和诊断治疗一体化方面取得了进展。本文将以IONP的MRI成像机理、制备和表面修饰为基础,阐述近年来IONP在MRI成像应用的研究成果和问题,期望IONP取得更好的发展。

关键词： 氧化铁纳米颗粒, 表面修饰, 成像机理, 磁共振成像应用

The application of Gd-based contrast agent is widely broad for magnetic resonance imaging in clinic diagnosis. However, the toxicity of Gd-based contrast agent still cannot be ignored. Therefore, most researchers have made a great effort to find low toxic contrast agent. Iron oxide nanoparticles(IONP) have a great dark contrast effects in magnetic resonance imaging(MRI) due to their superparamagnetic properties, and they also have good biocompatibility. With the rapid development of biomaterials and molecular image technology, the application of IONP in MRI has become more and more broad. In recent years, IONP has made great progress in dual-modal imaging. What’s more, IONP is not only used to clinical diagnosis, but also in treatment. It offers some new strategies for the treatment of disease. Based on the magnetic resonance imaging mechanism and preparation, surface modification of IONP, this review elaborates the research progress of IONP in magnetic resonance imaging in recent years.

Contents

1 Introduction

2 Magnetic resonance imaging principle

3 Development of MRI contrast agent

4 Preparation and modification of IONP

5 Application of IONP in MRI

5.1 Application of IONP in brain MRI

5.2 Application of IONP in liver MRI

5.3 Application of IONP in vessel MRI

5.4 Application of IONP molecular probe in MRI

5.5 Application of IONP in multimodal imaging

5.6 Application of IONP intelligent probe in MRI

5.7 Application of IONP in diagnosis and treatment

6 Conclusion and outlook

Key words: iron oxide nanoparticles(IONP), surface modification, imaging mechanism, MRI application
()
图1 MRI造影剂的发展[8~18]
Fig.1 The development of MRI contrast agent[8~18]
表1 IONP制备方法对比[19~23]
Table 1 Comparison of the preparation method of IONP[19~23]
Preparation Methods Advantages Disadvantages Surface Property ref
Coprecipitation Method Low needs of experiment conditions, short reaction time, easy to manipulate and low cost. Nonuniform diameter of products, large diameter and a poor monodispersity. Hydrophilia [19], [20]
Thermal Decomposition Method High crystallinity of products, uniform diameter and a good monodispersity. The products are hydrophobicity and need to further modify. Hydrophobicity [21]
Microemulsion Method Simple experimental installation, easy to manipulate and low energy consumption. Low productivity, low crystallinity of products, wide range of diameter distribution and high cost of solvent. Most of products are hydrophobicity. [22]
Hydrothermal Method Easy to manipulate, high purity of products and high magnetism. High requirements of reaction temperature, pressure and device. Hydrophilia [23]
表2 IONP修饰方法[26, 27, 32, 40]
Table 2 The modification methods of IONP[26, 27, 32, 40]
Modification methods Principle Commonly used substances ref
Amphiphilic ligand encapsulation The hydrophobic end of the amphiphilic polymer and the hydrophobic group on the surface of the nanoparticle form a micelle through Van der Waals hydrophobic interaction, and the hydrophilic group faces the outside of the particle, thereby obtaining water-dispersible nanoparticles. SiO2 PEG; Polysaccharose 27, 32
Ligand exchange Hydrophilic ligands with anchoring groups instead of hydrophobic surface ligands, thereby obtaining water-dispersible nanoparticles. Dopamine; Carboxylic 26,40
表3 IONP修饰物[28~34]
Table 3 The modifiers of IONP[28~34]
Modifiers Toxicity Function ref
Dextran Nontoxicity Dextran makes IONP have a good hydrophilia and dispersity. The surface carboxyls are easy to further functionalization. 28
PEG Low toxicity PEG can prevent IONP from aggregation, which makes IONP have a good dispersity. 27
Oleic acid Nontoxicity Oleic acid is absorbed in IONP using the polar end of negative charge, it prevents IONP from aggregation by repulsion between the same charge at the mean time, which makes IONP have a good dispersity. 40
Au Nontoxicity Au prevents IONP from external environment distribution and aggregation. It offers active surface for IONP to further functionalization as well. 31
SiO2 Nontoxicity SiO2 improves stability of IONP in hydrophilia solution, and it offers hydroxyl for IONP to further functionalization. 32
Polypeptide Nontoxicity Polypeptide linked to IONP make it acquire targetability for diseases, which could improve detection rate of diseases. 33, 34
图2 Fig.2 a) The TEM photos of GdIO nanoparticles, b) EDS mapping images of GdIO nanoparticles. c) T 1- and d) T 2-weighted in vivo MR images of BALB/c mice(top: coronal plane, bottom: transverse plane) before and after intravenous injection of GdIO nanoparticles. e) T 1- and f) T 2- weighted in vivo MR images of nude mice orthotopically inoculated with HepG2 liver cancer cells(sagittal plane) before and after intravenous injection of GdIO nanoparticles[40]
Fig.2
图3 a)颈动脉斑块患者和b)健康人注射USPIO前和注射72 h后R2*成像[43]
Fig.3 The R2* maps of a) patient with atherosclerotic plaque and b) healthy people after USPIO administration(72 h)[43]
图4 Fig.4 a) The TEM pictures of strawberry-like Fe3O4-Au NPs, b) the in vitro CT imaging effect of Au NPs strawberry-like Fe3O4-Au NPs, c) the in vitro MR imaging effect of strawberry-like Fe3O4-Au NPs, CT and T2-weighted MR imaging of d) fatty liver bearing rat, e) cirrhotic liver bearing rat and f) HCC bearing rat before and after Fe3O4-Au NPs administration [48]
Fig.4
图5 a)uIONP增强EPR效应的示意图,b)4T1原位瘤小鼠注射uIONP前后T 1加权成像和T 2加权成像[52]
Fig.5 a) The illustration of EPR effect enhancement by uIONP, b) T 1- and T 2-weighted MRI of a mouse bearing orthotopic 4T1 tumors before and after uIONP administration[52]
图6 Fig.6 a) Schematic illustration of the preparation and structure of FeAP-NPs, b) PA images of mice bearing tumors in vivo, c) MR images of mice bearing tumors in vivo, d) tumor growth curves after treatment in different methods, e) tumors images after treatment of 26 days [62]
Fig.6
图7 a)AuNW制备示意图,b)静脉注射AuNW前和2、4、24、48 h后超声和光声成像图,c)不同治疗组肿瘤体积变化曲线,d)不同治疗组生存曲线[63]
Fig.7 a) The illustration of AuNW preparation, b) ultrasonic and photoacoustic imaging pictures of AuNW before and at 2, 4, 24 and 48 h after intravenous injection of AuNW, c) tumor volume curves of different treatment groups, d) survival curves of different treatment groups[63]
图8 a) 基于MFION的MSCs中风后恢复治疗示意图,b) 1D MFION的透射电镜图片,c)MFION的体外成像效果,d)治疗前后脑梗死体积(黄箭头和红线标识)的MR检测(NT组:正常小鼠注射MSCs,Sham组:颈内动脉结扎但未阻塞,Na?ve组:MCAo鼠注射MSCs,PEI组:MCAo鼠注射PEI-MSCs,SPION组:MCAo鼠注射SPIO-MSCs,MFION:MCAo鼠注射MFION-MSCs)[64]
Fig.8 a) Schematic illustration of MFION-based engineering of MSCs for the recovery post-ischemic stroke. b) TEM pictures of 1D MFION, c) in vitro MR imaging effect of 1D MFION, d) MR detections of brain infarct volume(indicated by yellow arrows and red dash lines) before and after treatment.(NT group: MCAo mice without any treatment, Sham group:the internal carotid artery was ligated but no occlusion was performed, Na?ve group: MCAo mice treated with non-engineered MSCs, PEI group: MCAo mice treated with PEI-engineered MSCs, SPION group: MCAo mice treated with SPIO-engineered MSCs, MFION group: MCAo mice treated with MFION-engineered MSCs)[64]
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