Linear TACN-based cationic polymers as non-viral gene vectors

A series of linear cationic polymers were synthesized by the ring-opening polymerization between diglycidyl ethers and 1-Cbz-1,4,7-triazacyclononane (TACN). Besides the good pH buffering capacity in endosome pH range caused by TACN, these polymers have evenly distributed hydroxyl groups, which may benefit not only the water solubility but also their biocompatibility and serum tolerance. The polymers could condense DNA into nanoparticles with appropriate sizes and zeta-potentials. Cytotoxicity assays reveal that most of the polyplexes formed from title polymers have lower cytotoxicity than those derived from PEI. In vitro transfection assays show that some of these materials have higher transfection efficiency than bPEI, especially in tumor cells with the presence of serum. Flow cytometry and confocal microscopy were applied to further confirm their good serum tolerance. The structureactivity relationship of such type of polymeric vectors was also discussed. Results suggest that the ringopening polymerization may be an effective synthetic approach toward gene delivery materials with high biological activity.