Abstract
The lactosylated poly(1-vinylimidazole) (PVIm-Lac) with various lactosylated degrees has been synthesized for the co-delivery of zinc ions (Zn) and plasmid DNA (pDNA). The Zn/DNA/PVIm-Lac complex formation has achieved the specific delivery of zinc ions to HepG2 cells. Especially, the resulting hepatocyte-specific delivery of zinc ions has increased the number of insulin receptors on the cell surface. Consequently, the Zn/DNA/PVIm-Lac complexes have suppressed insulin receptor internalization on the surface of the HepG2 cells, expecting to offer unique therapy to inhibit hepatic insulin clearance.
Highlights
Zinc ion (Zn2+ ) is known to be an intracellular second messenger, like calcium ion (Ca2+ ), related to various biological functions [1,2,3]
More retardation of the plasmid DNA (pDNA) was especially5 of observed in the case of PVIm-Lac(20) at a positive/negative charge ratio of eight in the presence of Zn2+ ions, as compared to the absence of Zn2+ ions. These results suggest that the 2+ ions with PVIm-Lac(20), as well as PVIm-Lac(50) and PVIm-Lac(75), worked chelated retardedZn band of PVIm-Lac(75) exhibited no fluorescence
The number of Zn2+ ions inside human cervical cancer HeLa cells without asialoglycoprotein receptors was statistically significantly lower than that inside the HepG2 cells (p < 0.05). These results suggest that the zinc ions (Zn)/DNA/PVImLac(50) complexes with β-galactose residues were a suitable structure for cell-specific
Summary
Zinc ion (Zn2+ ) is known to be an intracellular second messenger, like calcium ion (Ca2+ ), related to various biological functions [1,2,3]. A cooperative function of insulin receptor substrates 1 and 2 are required for insulin signal transduction [13] These studies have inspired us to deliver Zn2+ ions to the liver in vivo for hepatic insulin clearance in the viewpoint of type 2 diabetes therapy. Through the use of each resulting PVIm-Lac, we mainly report the formation ability of the Zn2+ /pDNA/PVIm-Lac complex, that is, Zn/DNA/PVIm-Lac, followed by the determination of both the number of delivered intracellular Zn2+ ions and the number of insulin receptors on the surface of the HepG2 cells derived from human hepatocytes. From the above point of view, because ZnT8 is known to regulate hepatic insulin clearance [12], the optimization of hepatocyte-specific intracellular Zn2+ delivery systems are expected to be used for unique type 2 diabetes therapy without insulin injection. The hepatocyte-specific delivery of Zn2+ ions, based on our delivery systems, is considered to achieve no side effects and to offer facile pharmaceutical formulation, so this study is important for type 2 diabetes therapy
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