Preparation of Zn<sup>2+</sup>-Chelated Carboxymethyl Poly(1-Vinylimidazole) for Intracellular Zn<sup>2+</sup> Delivery

Abstract

Zinc ions (Zn 2+ ), known to be a novel intracellular second messenger related to various biological functions, have been delivered inside cells. For the intracellular Zn 2+ delivery, Zn 2+ has been chelated to carboxymethyl poly(1vinylimidazole) (CM-PVIm) by mixing zinc chloride (ZnCl 2 ) or zinc acetate (Zn(OAc) 2 ) with CM-PVIm. The resulting Zn 2+ -chelated CM-PVIm, that is, Zn 2+ /CM-PVIm complex by mixing ZnCl 2 exhibited smaller particle size below 10 nm and possessed larger amount of Zn 2+ ions, as compared to the Zn 2+ /CM-PVIm by mixing Zn(OAc) 2 . The both Zn 2+ /CM-PVIm complexes exhibited no significant cytotoxicity, leading to intracellular Zn 2+ delivery. The Zn 2+ /CM-PVIm by mixing ZnCl 2 delivered larger amount of intracellular Zn 2+ ions than that by mixing Zn(OAc) 2 . These results suggest that the optimal Zn 2+ /CM-PVIm complex is a useful tool for intracellular Zn 2+ delivery to control various biological functions.

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.…”

“…8 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) 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.…”

“…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 …”

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

“…We have previously reported on the design of lactosylated poly(1-vinylimidazole) (PVIm-Lac) for hepatocyte-specific plasmid DNA (pDNA) carriers [14]. Furthermore, we have also reported on Zn 2+ -chelated poly(1-vinylimidazole) (PVIm) derivatives for efficient pDNA delivery [15][16][17][18][19]. These pDNA delivery systems by Zn 2+ -chelated PVIm derivatives have succeeded in the co-delivery of Zn 2+ ions and pDNA, leading to enhancing the gene expression of the co-delivered pDNA.…”