Preparation of zinc-coordinated-DPA functionalized polyesters for gene condensation

Cationic polyesters have been widely utilized as efficient gene delivery carriers. Their ability in binding genes was majorly based on the electrostatic effect between the positive charges of polymers and the negatives charges of genes. It has been well known that large numbers of positive charges on the polymers would lead to undesired toxicity although strong gene binding capability. It was of great interest to developed a polymer with reduced positive charges while enhanced gene condensation ability. In this work, a library of polyesters functionalized by zinc-coordinated-dimethylpyridinium amine (DPA-Zn) have been successfully prepared by the polycondensation method starting from dimethyl 1,3-acetonedicarboxylate and 10 diols, followed by the post-modification using dimethylpyridinium amine and zinc nitrate. The post-modification efficiency was systemically evaluated and the optimized functionalization efficiency could reach around 50%. The gene condensation ability of the targeting polymers was also evaluated using gel retardation assay and dynamic light scatting. The results indicated that DPA-Zn functionalized polyesters could bind gene into nanocomplexes with the sizes around 200 nm.