Construction of Peptide-Lipoic Acid Cationic Polymers with Redox Responsiveness and Low Toxicity for Gene Delivery

As gene therapy continues to evolve, the development of safe and effective cationic polymer carriers is critical. In this work, three polymers have been prepared by ring-opening polymerization on the basis of peptide-lipoic acid monomers. By adjusting the sequence of the peptides, redox-responsive cationic polymers with different positive charge numbers were obtained, as well as investigating their performance as gene carriers. The results showed that the polymers complexed with negatively charged genes by electrostatic interaction and successfully transported the genes into the cells, additionally degrading and releasing the genes under glutathione (GSH) conditions. Furthermore, the polymers as gene carriers in different cell lines demonstrated lower cytotoxicity, with an excellent cell survival rate of 8 times higher than the "gold standard" polyethylenimine (PEI) at the same concentration. In vitro transfection experiments showed that the polymers successfully released and transfected genes into cells, demonstrating their immense potential in gene therapy.