Share：
Share this content in WeChat
X
[Chinese][PDF]2936
• Original Article •
Preparation of magnetic resonance T2 contrast agent Fe3O4@Cys and live imaging study of New Zealand rabbits
ZU Hanyu  CHEN Mengsha  HAN Huiting  YAN Peng  CHEN Liang  HUANG Yanan  ZHANG Juntao  JIANG Xingyue 

Cite this article as: ZU H Y, CHEN M S, HAN H T, et al. Preparation of magnetic resonance T2 contrast agent Fe3O4@Cys and live imaging study of New Zealand rabbits[J]. Chin J Magn Reson Imaging, 2023, 14(10): 105-110. DOI:10.12015/issn.1674-8034.2023.10.018.


[Abstract] Objective To prepare the magnetic resonance T2 contrast Fe3O4@Cys modified with cysteine (Cys) surface and tested by New Zealand rabbits using a 3.0 T magnetic resonance imaging system.Materials and Methods Using the solvent thermal method, different Fe3O4 nanoparticles were prepared by changing the reaction time and substrate concentration. The samples were characterized by X-ray diffractometer and their crystallinity were analyzed. The morphology and particle size of the samples were measured by scanning electron microscope. The samples with high crystallinity and uniform particle size were selected for surface modification with Cys. The surface potentials of Fe3O4, Fe3O4@Cys were measured by ZETA Potential Nanoparticle analyzer. The magnetic properties of Fe3O4 and Fe3O4@Cys were tested by vibration sample magnetometer. The cytotoxicity of the samples before and after modification was tested by MTT cell proliferation inhibition assay. The imaging performance was tested by observing signal changes in the renal cortex, medulla and small intestine at different time points before and after injection.Results When the amount of ferric chloride hexahydrate was 0.325 g, the Fe3O4 nanoparticles prepared for reaction at 200℃ temperature had high crystallization and uniform particle size. The average particle size was about 57.2 nm, the surface potential was -20 mV and-22 mV respectively. The particle size and morphology were not significantly changed, and the cell survival rate of Fe3O4@Cys was higher than 80%, which was higher than that of Fe3O4 group. The modified Fe3O4 nanoparticles exhibit superparamagnetism and have obvious negative contrast enhancement effect in magnetic resonance imaging in vivo.Conclusions As the reaction time increases, Fe3O4 crystallization increases; substrate concentration increases and Fe3O4 particle size decreases. Cys modification increases stability with biocompatibility and can be used as a T2 contrast agent for a variety of experimental and basic studies.
[Keywords] molecular imaging；ferriferrous oxide；contrast agent；nanomaterials；magnetic resonance imaging

ZU Hanyu1   CHEN Mengsha1   HAN Huiting1   YAN Peng2   CHEN Liang1   HUANG Yanan1   ZHANG Juntao3   JIANG Xingyue1*  

1 Department of Radiology, Affiliated Hospital of Binzhou Medical University, Binzhou 256600, China

2 Basic Medical College, Binzhou Medical University, Yantai 264003, China

3 GE Healthcare Shanghai Co., Ltd., Shanghai 201203, China

Corresponding author: JIANG X Y, E-mail: xyjiang188@sina.com

Conflicts of interest   None.

ACKNOWLEDGMENTS National Natural Science Foundation of China (No. 51401031); Shandong Province Natural Science Fund (No. ZR2018LH015).
Received  2023-03-24
Accepted  2023-09-25
DOI: 10.12015/issn.1674-8034.2023.10.018
Cite this article as: ZU H Y, CHEN M S, HAN H T, et al. Preparation of magnetic resonance T2 contrast agent Fe3O4@Cys and live imaging study of New Zealand rabbits[J]. Chin J Magn Reson Imaging, 2023, 14(10): 105-110. DOI:10.12015/issn.1674-8034.2023.10.018.

[1]
BONNET C S, TÓTH É. Metal-based environment-sensitive MRI contrast agents[J/OL]. Curr Opin Chem Biol, 2021, 61: 154-169 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/33706246/. DOI: 10.1016/j.cbpa.2021.01.013.
[2]
VAN ZANDWIJK J K, SIMONIS F F J, HESLINGA F G, et al. Comparing the signal enhancement of a gadolinium based and an iron-oxide based contrast agent in low-field MRI[J/OL]. PLoS One, 2021, 16(8): e0256252 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/34403442/. DOI: 10.1371/journal.pone.0256252.
[3]
KIM H K, LEE G H, CHANG Y M. Gadolinium as an MRI contrast agent[J]. Future Med Chem, 2018, 10(6): 639-661. DOI: 10.4155/fmc-2017-0215.
[4]
ZHAO Z H, LI M Y, ZENG J, et al. Recent advances in engineering iron oxide nanoparticles for effective magnetic resonance imaging[J/OL]. Bioact Mater, 2022, 12: 214-245 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/35310380/. DOI: 10.1016/j.bioactmat.2021.10.014.
[5]
XUE X D, BO R N, QU H J, et al. A nephrotoxicity-free, iron-based contrast agent for magnetic resonance imaging of tumors[J/OL]. Biomaterials, 2020, 257: 120234 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/32736259/. DOI: 10.1016/j.biomaterials.2020.120234.
[6]
GULANI V, CALAMANTE F, SHELLOCK F G, et al. Gadolinium deposition in the brain: summary of evidence and recommendations[J]. Lancet Neurol, 2017, 16(7): 564-570. DOI: 10.1016/S1474-4422(17)30158-8.
[7]
CHEN C, GE J X, GAO Y, et al. Ultrasmall superparamagnetic iron oxide nanoparticles: a next generation contrast agent for magnetic resonance imaging[J/OL]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2022, 14(1): e1740 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/34296533/. DOI: 10.1002/wnan.1740.
[8]
MA X H, CHEN K, WANG S, et al. Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model[J]. World J Gastrointest Oncol, 2022, 14(4): 858-871. DOI: 10.4251/wjgo.v14.i4.858.
[9]
ULBRICH K, HOLÁ K, ŠUBR V, et al. Targeted drug delivery with polymers and magnetic nanoparticles: covalent and noncovalent approaches, release control, and clinical studies[J]. Chem Rev, 2016, 116(9): 5338-5431. DOI: 10.1021/acs.chemrev.5b00589.
[10]
GAVILÁN H, AVUGADDA S K, FERNÁNDEZ-CABADA T, et al. Magnetic nanoparticles and clusters for magnetic hyperthermia: optimizing their heat performance and developing combinatorial therapies to tackle cancer[J]. Chem Soc Rev, 2021, 50(20): 11614-11667. DOI: 10.1039/d1cs00427a.
[11]
LIU L J, LIU L, LI Y, et al. Ultrasmall superparamagnetic nanoparticles targeting E-selectin: synthesis and effects in mice in vitro and in vivo[J/OL]. Int J Nanomedicine, 2019, 14: 4517-4528 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/31354271/. DOI: 10.2147/IJN.S199571.
[12]
ZHU X L, LU N, ZHOU Y, et al. Targeting pancreatic cancer cells with peptide-functionalized polymeric magnetic nanoparticles[J/OL]. Int J Mol Sci, 2019, 20(12): 2988 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/31248076/. DOI: 10.3390/ijms20122988.
[13]
FU Y, ZHAO W L, LIN K X, et al. USPIO-SWI shows fingolimod enhanced alteplase action on angiographic reperfusion in eMCAO rats[J]. J Magn Reson Imaging, 2022, 55(4): 1095-1106. DOI: 10.1002/jmri.27914.
[14]
BUCH S, CHEN Y S, JELLA P, et al. Vascular mapping of the human hippocampus using Ferumoxytol-enhanced MRI[J/OL]. NeuroImage, 2022, 250: 118957 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/35122968/. DOI: 10.1016/j.neuroimage.2022.118957.
[15]
PHILIPS B W J, STIJNS R C H, RIETSCH S H G, et al. USPIO-enhanced MRI of pelvic lymph nodes at 7-T: preliminary experience[J]. Eur Radiol, 2019, 29(12): 6529-6538. DOI: 10.1007/s00330-019-06277-7.
[16]
STIJNS R C H, PHILIPS B W J, NAGTEGAAL I D, et al. USPIO-enhanced MRI of lymph nodes in rectal cancer: a node-to-node comparison with histopathology[J/OL]. Eur J Radiol, 2021, 138: 109636 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/33721766/. DOI: 10.1016/j.ejrad.2021.109636.
[17]
LIU Q M, LIU L J, MO C W, et al. Polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X nanotheranostic platform for nasopharyngeal carcinoma imaging and photothermal therapy[J/OL]. J Nanobiotechnology, 2021, 19(1): 171 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/34103070/. DOI: 10.1186/s12951-021-00918-0.
[18]
CAZELLES A, COLLARD M K, LALATONNE Y, et al. A preclinical validation of iron oxide nanoparticles for treatment of perianal fistulizing Crohn's disease[J/OL]. Int J Mol Sci, 2022, 23(15): 8324 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/35955465/. DOI: 10.3390/ijms23158324.
[19]
LU G L, LIN Y C, WU P C, et al. The surface amine group of ultrasmall magnetic iron oxide nanoparticles produce analgesia in the spinal cord and decrease long-term potentiation[J/OL]. Pharmaceutics, 2022, 14(2): 366 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/35214098/. DOI: 10.3390/pharmaceutics14020366.
[20]
ZHANG C Y, HUANG W T, HUANG C, et al. VHPKQHR peptide modified ultrasmall paramagnetic iron oxide nanoparticles targeting rheumatoid arthritis for T1-weighted magnetic resonance imaging[J/OL]. Front Bioeng Biotechnol, 2022, 10: 821256 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/35295653/. DOI: 10.3389/fbioe.2022.821256.
[21]
DADFAR S M, ROEMHILD K, DRUDE N I, et al. Iron oxide nanoparticles: diagnostic, therapeutic and theranostic applications[J/OL]. Adv Drug Deliv Rev, 2019, 138: 302-325 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/30639256/. DOI: 10.1016/j.addr.2019.01.005.
[22]
MOHAMMADI A, BARIKANI M, LAKOURAJ M M. Biocompatible polyurethane/thiacalix[4]arenes functionalized Fe3O4 magnetic nanocomposites: synthesis and properties[J/OL]. Mater Sci Eng C Mater Biol Appl, 2016, 66: 106-118 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/27207044/. DOI: 10.1016/j.msec.2016.04.064.
[23]
SONG C, SUN W J, XIAO Y C, et al. Ultrasmall iron oxide nanoparticles: synthesis, surface modification, assembly, and biomedical applications[J]. Drug Discov Today, 2019, 24(3): 835-844. DOI: 10.1016/j.drudis.2019.01.001.
[24]
BELKAHLA H, ANTUNES J C, LALATONNE Y, et al. USPIO-PEG nanoparticles functionalized with a highly specific collagen-binding peptide: a step towards MRI diagnosis of fibrosis[J]. J Mater Chem B, 2020, 8(25): 5515-5528. DOI: 10.1039/d0tb00887g.
[25]
WU J, WU T, CHEN P, et al. Study of Fe3O4-PPy core-shell nanocomposite in the diagnosis of tumor markers in the tissues of early gastric cancer patients[J]. J Nanosci Nanotechnol, 2021, 21(2): 935-942. DOI: 10.1166/jnn.2021.18684.
[26]
RASHIDI DAFEH S, IRANMANESH P, SALARIZADEH P. Fabrication, optimization, and characterization of ultra-small superparamagnetic Fe3O4 and biocompatible Fe3O4@ZnS core/shell magnetic nanoparticles: ready for biomedicine applications[J/OL]. Mater Sci Eng C Mater Biol Appl, 2019, 98: 205-212 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/30813021/. DOI: 10.1016/j.msec.2018.12.147.
[27]
ALBALAWI A E, KHALAF A K, ALYOUSIF M S, et al. Fe3O4@piroctone olamine magnetic nanoparticles: Synthesize and therapeutic potential in cutaneous leishmaniasis[J/OL]. Biomedecine Pharmacother, 2021, 139: 111566 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/33839494/. DOI: 10.1016/j.biopha.2021.111566.
[28]
OGNJANOVIĆ M, RADOVIĆ M, MIRKOVIĆ M, et al. 99mTc-, 90Y-, and 177Lu-labeled iron oxide nanoflowers designed for potential use in dual magnetic hyperthermia/radionuclide cancer therapy and diagnosis[J]. ACS Appl Mater Interfaces, 2019, 11(44): 41109-41117. DOI: 10.1021/acsami.9b16428.
[29]
WU C, ZHANG G Z, WANG Z H, et al. Macrophage-mediated delivery of Fe3O4-nanoparticles: a generalized strategy to deliver iron to tumor microenvironment[J]. Curr Drug Deliv, 2022, 19(9): 928-939. DOI: 10.2174/1567201819666220426085450.
[30]
MENG Q F, RAO L, ZAN M H, et al. Macrophage membrane-coated iron oxide nanoparticles for enhanced photothermal tumor therapy[J/OL]. Nanotechnology, 2018, 29(13): 134004 [2023-03-23]. https://pubmed.ncbi.nlm.nih.gov/29334363/. DOI: 10.1088/1361-6528/aaa7c7.
[31]
SUN X C, LYU S G. L-cysteine-modified Fe3 O4 nanoparticles as a novel heterogeneous catalyst for persulfate activation on BTEX removal[J]. Water Environ Res, 2021, 93(12): 3023-3036. DOI: 10.1002/wer.1654.
[32]
FENG X Y, DENG C H, GAO M X, et al. Facile and easily popularized synthesis of L-cysteine-functionalized magnetic nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides[J]. Anal Bioanal Chem, 2018, 410(3): 989-998. DOI: 10.1007/s00216-017-0602-5.
[33]
ZHAO H, SENE S, MIELCAREK A M, et al. Hierarchical superparamagnetic metal-organic framework nanovectors as anti-inflammatory nanomedicines[J]. J Mater Chem B, 2023, 11(14): 3195-3211. DOI: 10.1039/d2tb02094g.
[34]
XU P J, FENG X, WANG L J, et al. Preparation of carboxylated superparamagnetic Fe3O4 nanoparticles by solvothermal method and its magnetochromism[J]. J Funct Mater, 2021, 52(1): 1026-1032. DOI: 10.3969/j.issn.1001-9731.2021.01.005.
[35]
NATALIA M, TOMASZ O, ZYGMUNT M, et al. Ostwald ripening in an oxide-on-metal system[J/OL]. Adv Mater Interfaces, 2022, 9(17) [2023-03-23]. https://scholar.cnki.net/zn/Detail/index/GARJ2021_3/SJWDBA32232F4456EE848D251E5DFAED3FC9. DOI: 10.1002/ADMI.202200222.
[36]
ZHAN H D, DIAO C C, ZHAO M M, et al. Preparation and properties of iron-soy protein nano complexes based on coordination[J]. Food Sci, 2023, 44(8): 1-8. DOI: 10.7506/spkx1002-6630-20220806-080.
[37]
WANG C L, ZHAO Y L, ZHAO J F. Recent advances in chemical protein modification via cysteine[J]. Chin J Org Chem, 2022, 42(9): 2774-2792. DOI: 10.6023/cjoc202203008.
[38]
HUANG L Q, SHI X M, WANG J R, et al. Preparation and polarization activity research of astragalus polysaccharide-superparamagnetic iron oxide nanocomposite[J]. Acta Pharm Sin, 2023, 58(3): 779-788. DOI: 10.16438/j.0513-4870.2022-1059.
[39]
SONG J, GE R, ZHU K, et al. Application of magnetic nanoparticles in vitro MRI of mouse macrophages[J]. Chin J Magn Reson Imag, 2022, 13(2): 57-61. DOI: 10.12015/issn.1674-8034.2022.02.012.
[40]
XIE Z J. Macrophage heterogeneity[J]. Med Recapitul, 2001, 7(6): 367-370. DOI: 10.3969/j.issn.1006-2084.2001.06.025.

PREV Nomogram based on clinical, pathological, and DWI quantitative parameters for predicting the programmed death-ligand 1 positive expression in cervical cancer: Comparison of different ROI options
NEXT Application value of intelligent quick magnetic resonance technique in magnetic resonance scanning of cervical vertebra
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn