Degradable polyesters via ring-opening polymerization of functional valerolactones for efficient gene delivery

Abstract

Degradable polymers as gene and drug carriers are emerging as one of the most promising types of materials in the biomedical and pharmaceutical areas. Herein, we report the synthesis of a series of block co-polyesters (B1-B6) and random co-polyesters (C1-C4) via ring-opening polymerization of tertiary amine-bearing valerolactone and alkylated valerolactone monomers. These polymers can completely inhibit the electrophoretic migrations of plasmid DNAs (pDNAs) at a w/w ratio of 2-6. The polyplexes of these polymers with pDNAs were steadily formed in a narrow range of sizes (75 to 220 nm) and could be effectively internalized into the cytoplasm. The results of transfection experiments showed that the block copolymers generally exhibited better performance than their random counterparts and the aliphatic chain lengths on the backbone of the polymers obviously affected the transfection efficiency (TE). Block copolymer B5 with n-octyl chains generated the best TE in Hek293T cells, which was 2.2 fold that of polyethylenimine (PEI) 25k under the optimal conditions. Moreover, these polymers were found to be more biocompatible compared to PEI 25k, and showed degradable properties. Our results suggest that these polymers are potentially reliable/efficient non-viral gene vectors.