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

The co-delivery system of zinc ions (Zn2+) and plasmid DNA (pDNA) has been designed by the use of poly(1-vinylimidazole) (PVIm) derivatives for myoblast differentiation. Six PVIm derivatives were synthesized, followed by the optimization of the chemical structure. As a result, methylated and carboxymethylated PVIm (CM-PVIm-Me) delivered the highest amount of Zn2+ ions inside C2C12 myoblast cells. The CM-PVIm-Me also delivered pDNA inside the myoblast cells to exhibit pDNA gene expression which was upregulated by the co-delivered Zn2+ ions. The co-delivered Zn2+ ions were localized in the cell nucleus presumably to affect cellular functions. Actually, the myoblast cells treated with the Zn2+/CM-PVIm-Me/pDNA complexes differentiated to myotubes. These results suggest that the Zn2+ ions delivered by the CM-PVIm-Me inside the cells differentiated myoblasts to myotubes. Our co-delivery system of Zn2+ ion and pDNA without zinc transporter can be a unique tool of regenerative medicine for muscular injury.