Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells

To specifically detect and trace transplanted islet β-cells by magnetic resonance imaging (MRI), we conjugated manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) with exendin-4 (Ex4) which specifically binds glucagon-like peptide-1 receptors on the surface of β-cells. The size dist...

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Autores principales:	Jyuhn-Huarng Juang, Chia-Rui Shen, Jiun-Jie Wang, Shu-Ting Wu, Sung-Han Lin, Chen-Yi Chen, Chen-Wei Kao, Chen-Ling Chen, Zei-Tsan Tsai, Yun-Ming Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	islet transplantation manganese magnetism-engineered iron oxide nanoparticles exendin-4 magnetic resonance images Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/a241877824bc4e03916e477d2be9d760
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spelling	oai:doaj.org-article:a241877824bc4e03916e477d2be9d7602021-11-25T18:32:46ZExendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells10.3390/nano111131452079-4991https://doaj.org/article/a241877824bc4e03916e477d2be9d7602021-11-01T00:00:00Zhttps://www.mdpi.com/2079-4991/11/11/3145https://doaj.org/toc/2079-4991To specifically detect and trace transplanted islet β-cells by magnetic resonance imaging (MRI), we conjugated manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) with exendin-4 (Ex4) which specifically binds glucagon-like peptide-1 receptors on the surface of β-cells. The size distribution of MnMEIO and MnMEIO-Ex4 NPs were 67.8 ± 1.3 and 70.2 ± 2.3 nm and zeta potential 33.3 ± 0.5 and 0.6 ± 0.1 mV, respectively. MnMEIO and MnMEIO-Ex4 NPs with iron content ≤ 40 μg/mL did not affect MIN6 β-cell viability and insulin secretion. Positive iron staining was found in MIN6 β-cells loaded with MnMEIO-Ex4 NPs but not in those with MnMEIO NPs. A transmission electron microscope confirmed MnMEIO-Ex4 NPs were distributed in the cytoplasm of MIN6. In vitro MR images revealed a loss of signal intensity in MIN6 β-cells labeled with MnMEIO-Ex4 NPs but not with MnMEIO NPs. After transplantation of islets labeled with MnMEIO-Ex4, the graft under kidney capsule could be visualized on MRI as persistent hypointense areas up to 17 weeks. Moreover, histology of the islet graft showed positive staining for insulin, glucagon and iron. Our results indicate MnMEIO-Ex4 NPs are safe and effective for the detection and long-term monitoring of transplanted β-cells by MRI.Jyuhn-Huarng JuangChia-Rui ShenJiun-Jie WangShu-Ting WuSung-Han LinChen-Yi ChenChen-Wei KaoChen-Ling ChenZei-Tsan TsaiYun-Ming WangMDPI AGarticleislet transplantationmanganese magnetism-engineered iron oxide nanoparticlesexendin-4magnetic resonance imagesChemistryQD1-999ENNanomaterials, Vol 11, Iss 3145, p 3145 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	islet transplantation manganese magnetism-engineered iron oxide nanoparticles exendin-4 magnetic resonance images Chemistry QD1-999
spellingShingle	islet transplantation manganese magnetism-engineered iron oxide nanoparticles exendin-4 magnetic resonance images Chemistry QD1-999 Jyuhn-Huarng Juang Chia-Rui Shen Jiun-Jie Wang Shu-Ting Wu Sung-Han Lin Chen-Yi Chen Chen-Wei Kao Chen-Ling Chen Zei-Tsan Tsai Yun-Ming Wang Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells
description	To specifically detect and trace transplanted islet β-cells by magnetic resonance imaging (MRI), we conjugated manganese magnetism-engineered iron oxide nanoparticles (MnMEIO NPs) with exendin-4 (Ex4) which specifically binds glucagon-like peptide-1 receptors on the surface of β-cells. The size distribution of MnMEIO and MnMEIO-Ex4 NPs were 67.8 ± 1.3 and 70.2 ± 2.3 nm and zeta potential 33.3 ± 0.5 and 0.6 ± 0.1 mV, respectively. MnMEIO and MnMEIO-Ex4 NPs with iron content ≤ 40 μg/mL did not affect MIN6 β-cell viability and insulin secretion. Positive iron staining was found in MIN6 β-cells loaded with MnMEIO-Ex4 NPs but not in those with MnMEIO NPs. A transmission electron microscope confirmed MnMEIO-Ex4 NPs were distributed in the cytoplasm of MIN6. In vitro MR images revealed a loss of signal intensity in MIN6 β-cells labeled with MnMEIO-Ex4 NPs but not with MnMEIO NPs. After transplantation of islets labeled with MnMEIO-Ex4, the graft under kidney capsule could be visualized on MRI as persistent hypointense areas up to 17 weeks. Moreover, histology of the islet graft showed positive staining for insulin, glucagon and iron. Our results indicate MnMEIO-Ex4 NPs are safe and effective for the detection and long-term monitoring of transplanted β-cells by MRI.
format	article
author	Jyuhn-Huarng Juang Chia-Rui Shen Jiun-Jie Wang Shu-Ting Wu Sung-Han Lin Chen-Yi Chen Chen-Wei Kao Chen-Ling Chen Zei-Tsan Tsai Yun-Ming Wang
author_facet	Jyuhn-Huarng Juang Chia-Rui Shen Jiun-Jie Wang Shu-Ting Wu Sung-Han Lin Chen-Yi Chen Chen-Wei Kao Chen-Ling Chen Zei-Tsan Tsai Yun-Ming Wang
author_sort	Jyuhn-Huarng Juang
title	Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells
title_short	Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells
title_full	Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells
title_fullStr	Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells
title_full_unstemmed	Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells
title_sort	exendin-4-conjugated manganese magnetism-engineered iron oxide nanoparticles as a potential magnetic resonance imaging contrast agent for tracking transplanted β-cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a241877824bc4e03916e477d2be9d760
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Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells

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