Cell line dependent uptake and transfection efficiencies of PEI-anionic glycopolymer systems

Branched Poly(ethylenimine) (bPEI) is a commercially available cationic polymer, which is well-studied due to its superior gene transfection efficacies. However, its toxicity is a major concern for its use in clinical applications. Therefore, bPEI is modified with various non-ionic, non-toxic moieties in an effort to reduce its toxicity. Ternary complexes of PEI with anionic polymers have also been used to decrease its toxicity. In this report, we have prepared pH-sensitive glycopolymers of linear and hyperbranched architecture via reversible addition-fragmentation chain transfer polymerization (RAFT). These anionic glycopolymers were complexed with bPEI at varying weight by weight (w/w) ratios to reduce the toxicity of PEI in vitro. In addition, these PEI-anionic glycopolymer complexes showed improved buffering capacity, as compared to PEI alone. The interactions of anionic glycopolymers with Hep G2 and HEK 293T cells were then studied as a function of time. The cellular uptake and gene expression of PEI polyplexes in the presence of anionic glycopolymers was directly related to the interactions of anionic glycopolymers with Hep G2 and HEK 293T cells.