Cationic cross-linked polymers containing labile disulfide and boronic ester linkages for effective triple responsive DNA release

Abstract Disruption of DNA carriers triggered by intracellular bio-stimulants has been broadly considered as most convenient strategy for efficient DNA delivery. In this direction, we have designed and synthesized pH, redox and ATP responsive cationic cross-linked polymers (CLPs) having disulfide and reversible boronic ester linkages. These CLPs also contain folate groups that are known for their targeting capability towards cancer cells. Biophysical studies showed that these cationic CLPs exhibited more effective DNA condensation in comparison to cationic linear polymers resulting in the formation of nano-sized polyplexes with sufficient positive zeta potentials and good colloidal stability at neutral pH (∼7.4). More interestingly, the polyplexes prepared from these CLPs have the ability to selectively release complexed DNA under conditions similar to those prevalent in cancer cells such as acidic pH, ATP rich surroundings or presence of glutathione, as revealed by ethidium bromide exclusion assay, agarose gel electrophoresis, AFM measurements, etc. Therefore, these cross-linked polymers have high potential of being effective non-viral gene delivery vehicles.