Hepatocyte-Specific Co-Delivery of Zinc Ions and Plasmid DNA by Lactosylated Poly(1-vinylimidazole) for Suppression of Insulin Receptor Internalization

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.

Design of the Zinc Ion and Plasmid DNA Co-Delivery System by Poly(1-Vinylimidazole) Derivatives for Myoblast Differentiation

“…Then, the imidazole groups of the PVIm was quarternized without cross-linking. The resulting quaternized PVIm derivatives (R1 in Figure 1) were PVIm-Me 11,12 (methylation degree: 8 and 28 mol %), CM-PVIm 13 (carboxymethylation degree: 29 and 68 mol %), and PVIm-Pr-NH 2 14 (aminopropylation degree: 29 mol %) (Figure S1). Furthermore, the resulting CM-PVIm derivatives (R2 in Figure 1) were CM-PVIm-Me (carboxymethylation and methylation degree: 40 and 28 mol %, respectively) (Figure S2), CM-PVIm-Spe (carboxymethylation and spermine modification degree: 42 and 26 mol %, respectively) (Figure S3), and CM-PVIm-PEG (carboxymethylation and PEGylation degree: 19 and 11 mol %, respectively) (Figure S4).…”

“…In this study, based on the above backbone polymer, − we have designed the Zn 2+ ions and pDNA co-delivery system by PVIm derivatives for myoblast differentiation to myotube, expecting the myogenesis of skeletal muscle. Zn 2+ ions are known to bind imidazole groups of the PVIm-R, resulting in the formation of Zn 2+ /PVIm-R/pDNA polyion complexes, although Zn 2+ ions without PVIm-R cannot form the polyion complex with pDNA. , This manuscript is mainly focused on the optimization of the chemical structure of PVIm derivatives and the delivery function of Zn 2+ ions as well as pDNA, so the detailed mechanism of myoblast differentiation is out of the scope of the present study.…”

“…We have already reported the co-delivery system of Zn 2+ ions and pDNA by use of poly(1-vinylimidazole) (PVIm) 9,10 derivatives such as alkylated PVIm (PVIm-R), 11,12 carboxymethyl PVIm (CM-PVIm), 13 and aminopropylated PVIm (PVIm-Pr-NH 2 ) modified with lactose. 14 In this study, based on the above backbone polymer, 11−14 we have designed the Zn 2+ ions and pDNA co-delivery system by PVIm derivatives for myoblast differentiation to myotube, expecting the myogenesis of skeletal muscle. Zn 2+ ions are known to bind imidazole groups of the PVIm-R, resulting in the formation of Zn 2+ /PVIm-R/pDNA polyion complexes, although Zn 2+ ions without PVIm-R cannot form the polyion complex with pDNA.…”

“…Therefore, the skeletal muscle is considered to be an attractive target to deliver Zn 2+ ions and pDNA for QOL. We have already reported the co-delivery system of Zn 2+ ions and pDNA by use of poly­(1-vinylimidazole) (PVIm) , derivatives such as alkylated PVIm (PVIm-R), , carboxymethyl PVIm (CM-PVIm), and aminopropylated PVIm (PVIm-Pr-NH 2 ) modified with lactose …”