Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging

Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging

Ya-Wen Chen,1,2 Gunn-Guang Liou,3 Huay-Ben Pan,4,5 Hui-Hwa Tseng,5,6 Yu-Ting Hung,4 Chen-Pin Chou4,5,7,8 1National Institute of Cancer Research, National Health Research Institutes, Miaoli, 2Graduate Institute of Basic Medical Science, China Medical University, Taichung, 3Institute of Molecular and...

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Autores principales: Chen YW, Liou GG, Pan HB, Tseng HH, Hung YT, Chou CP
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2015
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Medicine (General)
R5-920
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spelling oai:doaj.org-article:e00920cd5a7b489aa7b53bb14fe5e1342021-12-02T07:28:30ZSpecific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging1178-2013https://doaj.org/article/e00920cd5a7b489aa7b53bb14fe5e1342015-11-01T00:00:00Zhttps://www.dovepress.com/specific-detection-of-cd133-positive-tumor-cells-with-iron-oxide-nanop-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ya-Wen Chen,1,2 Gunn-Guang Liou,3 Huay-Ben Pan,4,5 Hui-Hwa Tseng,5,6 Yu-Ting Hung,4 Chen-Pin Chou4,5,7,8 1National Institute of Cancer Research, National Health Research Institutes, Miaoli, 2Graduate Institute of Basic Medical Science, China Medical University, Taichung, 3Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, 4Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, 5School of Medicine, National Yang-Ming University, Taipei, 6Department of Pathology, Kaohsiung Veterans General Hospital, Kaohsiung, 7Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, 8School of Medicine, National Defense Medical Center, Taipei, Taiwan Background: The use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to visualize cells has been applied clinically, showing the potential for monitoring cells in vivo with magnetic resonance imaging (MRI). USPIO conjugated with anti-CD133 antibodies (USPIO-CD133 Ab) that recognize the CD133 molecule, a cancer stem cell marker in a variety of cancers, was studied as a novel and potent agent for MRI contrast enhancement of tumor cells. Materials and methods: Anti-CD133 antibodies were used to conjugate with USPIO via interaction of streptavidin and biotin for in vivo labeling of CD133-positive cells in xenografted tumors and N-ethyl-N-nitrosourea (ENU)-induced brain tumors. The specific binding of USPIO-CD133 Ab to CD133-positive tumor cells was subsequently detected by Prussian blue staining and MRI with T2-weighted, gradient echo and multiple echo recombined gradient echo images. In addition, the cellular toxicity of USPIO-CD133 Ab was determined by analyzing cell proliferation, apoptosis, and reactive oxygen species production. Results: USPIO-CD133 Ab specifically recognizes in vitro and labels CD133-positive cells, as validated using Prussian blue staining and MRI. The assays of cell proliferation, apoptosis, and reactive oxygen species production showed no significant differences in tumor cells with or without labeling of USPIO-CD133 Ab. In vivo imaging of CD133-positive cells was demonstrated by intravenous injection of USPIO-CD133 Ab in mice with HT29 xenografted tumors. The MRI of HT29 xenografts showed several clusters of hypotensive regions that correlated with CD133 expression and Prussian blue staining for iron. In rat, brain tumors induced by transplacental ENU mutagenesis, several clusters of hypointensive zones were observed in CD133-expressing brain tumors by MRI and intravenously administered USPIO-CD133 Ab. Conclusion: Combination of USPIO-CD133 Ab and MRI is valuable in recognizing CD133-expressing tumor cells in vitro, extracellularly labeling for cell tracking and detecting CD133-expressing tumors in xenografted tumors as well as ENU-induced rat brain tumors. Keywords: MRI, USPIO, CD133, USPIO-CD133 Ab, molecular imagingChen YWLiou GGPan HBTseng HHHung YTChou CPDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 6997-7018 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Chen YW
Liou GG
Pan HB
Tseng HH
Hung YT
Chou CP
Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging
description Ya-Wen Chen,1,2 Gunn-Guang Liou,3 Huay-Ben Pan,4,5 Hui-Hwa Tseng,5,6 Yu-Ting Hung,4 Chen-Pin Chou4,5,7,8 1National Institute of Cancer Research, National Health Research Institutes, Miaoli, 2Graduate Institute of Basic Medical Science, China Medical University, Taichung, 3Institute of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, 4Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, 5School of Medicine, National Yang-Ming University, Taipei, 6Department of Pathology, Kaohsiung Veterans General Hospital, Kaohsiung, 7Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, 8School of Medicine, National Defense Medical Center, Taipei, Taiwan Background: The use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to visualize cells has been applied clinically, showing the potential for monitoring cells in vivo with magnetic resonance imaging (MRI). USPIO conjugated with anti-CD133 antibodies (USPIO-CD133 Ab) that recognize the CD133 molecule, a cancer stem cell marker in a variety of cancers, was studied as a novel and potent agent for MRI contrast enhancement of tumor cells. Materials and methods: Anti-CD133 antibodies were used to conjugate with USPIO via interaction of streptavidin and biotin for in vivo labeling of CD133-positive cells in xenografted tumors and N-ethyl-N-nitrosourea (ENU)-induced brain tumors. The specific binding of USPIO-CD133 Ab to CD133-positive tumor cells was subsequently detected by Prussian blue staining and MRI with T2-weighted, gradient echo and multiple echo recombined gradient echo images. In addition, the cellular toxicity of USPIO-CD133 Ab was determined by analyzing cell proliferation, apoptosis, and reactive oxygen species production. Results: USPIO-CD133 Ab specifically recognizes in vitro and labels CD133-positive cells, as validated using Prussian blue staining and MRI. The assays of cell proliferation, apoptosis, and reactive oxygen species production showed no significant differences in tumor cells with or without labeling of USPIO-CD133 Ab. In vivo imaging of CD133-positive cells was demonstrated by intravenous injection of USPIO-CD133 Ab in mice with HT29 xenografted tumors. The MRI of HT29 xenografts showed several clusters of hypotensive regions that correlated with CD133 expression and Prussian blue staining for iron. In rat, brain tumors induced by transplacental ENU mutagenesis, several clusters of hypointensive zones were observed in CD133-expressing brain tumors by MRI and intravenously administered USPIO-CD133 Ab. Conclusion: Combination of USPIO-CD133 Ab and MRI is valuable in recognizing CD133-expressing tumor cells in vitro, extracellularly labeling for cell tracking and detecting CD133-expressing tumors in xenografted tumors as well as ENU-induced rat brain tumors. Keywords: MRI, USPIO, CD133, USPIO-CD133 Ab, molecular imaging
format article
author Chen YW
Liou GG
Pan HB
Tseng HH
Hung YT
Chou CP
author_facet Chen YW
Liou GG
Pan HB
Tseng HH
Hung YT
Chou CP
author_sort Chen YW
title Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging
title_short Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging
title_full Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging
title_fullStr Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging
title_full_unstemmed Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging
title_sort specific detection of cd133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/e00920cd5a7b489aa7b53bb14fe5e134
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