Exendin-4-Conjugated Manganese Magnetism-Engineered Iron Oxide Nanoparticles as a Potential Magnetic Resonance Imaging Contrast Agent for Tracking Transplanted β-Cells
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
Affiliations
Jyuhn-Huarng Juang
Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Chia-Rui Shen
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Jiun-Jie Wang
Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Shu-Ting Wu
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Sung-Han Lin
Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
Chen-Yi Chen
Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Chen-Wei Kao
Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Chen-Ling Chen
Division of Endocrinology and Metabolism, Department of Internal Medicine and Center for Tissue Engineering, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
Zei-Tsan Tsai
Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan 33302, Taiwan
Yun-Ming Wang
Department of Biological Science and Technology, Institute of Molecular Medicine and Bioengineering, Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu 300, Taiwan
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.
