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 beta-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 beta-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 mu g/mL did not affect MIN6 beta-cell viability and insulin secretion. Positive iron staining was found in MIN6 beta-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 beta-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 beta-cells by MRI.

Automated summary

The study successfully conjugated manganese magnetism-engineered iron oxide nanoparticles with exendin-4 to specifically detect and trace transplanted islet beta-cells by MRI. The method showed no adverse effects on cell viability and secretion, allowing for long-term monitoring of transplanted beta-cells.