Retracted Article: A multifunctional self-dissociative polyethyleneimine derivative coating polymer for enhancing the gene transfection efficiency of DNA/polyethyleneimine polyplexes in vitro and in vivo†
A new pH-responsive charge-conversion and rapidly self-dissociative multifunctional polymer lauric acid-polyethyleneimine-cyclohexanedicarboxylic anhydride-folic acid (LA-PEI-HHPA-FA, LPHF) is developed. LPHF as an amide with neighboring carboxylic acid groups becomes negatively charged at physiological pH and was used as a coating polymer to shield positively charged DNA/polyethyleneimine 25 k (DP) binary polyplexes, resulting in the formation of DPLPHF ternary polyplexes. The characterization using various methods proved that DPLPHF ternary polyplexes are stable at physiological pH, while in acidic endosomes, the coating polymer LPHF could quickly self-dissociate from the DP binary polyplexes. As compared with DP binary polyplexes, DPLPHF ternary polyplexes containing the tumor targeting ligand folic acid (FA), the absorption enhancer lauric acid (LA) and the charge-conversion entity cis-1,2-cyclohexanedicarboxylic anhydride (HHPA) exhibited more effective cellular uptake and higher transfection efficiency with lower non-therapeutic cytotoxicity in vitro. Moreover, in vivo studies revealed the significantly stronger tumor targeting and tumor inhibiting efficacy of DPLPHF ternary polyplexes. All these findings demonstrated the potential of LPHF as a promising coating polymer for enhanced gene transfection efficiency of DP binary polyplexes in vitro and in vivo.