Guanidinated multi-arm star polyornithines with a polyethylenimine core for gene delivery

- Multi-arm star polymers are prepared by grafting polyornithine arms on a PEI core.
- The polyornithine arms are partially guanidinated to form arginine units.
- The polymers are almost as efficient as 25 kDa PEI for gene delivery in 293T cells.
- The guanidinated polymers show improved serum-compatibility in gene delivery.

Multi-arm star polyornithines PEI-P(Orn)n are prepared by grafting polyornithine arms onto branched polyethylenimine (PEI) with an Mw of 600 via the ring-opening polymerization of N-carboxyanhydride of benzyloxycarbonyl ornithine. To enhance gene delivery efficiency and reduce cytotoxicity, the amino side groups on the polyornithine arms are partially guanidinated that transforms the ornithine units to arginine units. Thus, the guanidinated products G-PEI-P(Orn)n contain multiple poly(ornithine-co-arginine) arms. PEI-P(Orn)n and G-PEI-P(Orn)71 mediate the transfection of pGL3 plasmid to 293T cells almost as efficient as 25 kDa PEI in serum-free medium. Notably, in contrast to the dramatically lowered efficiency of 25 kDa PEI in the presence of serum, the efficiency of G-PEI-P(Orn)71 can be retained or even enhanced in the medium containing 10% serum. The improved serum-compatibility and high efficiency of the guanidinium-modified star polyornithines make them promising for gene delivery.