Yun Hui, Wang Kang, Zhang Jun, Peng Guofeng, Zhao Hui
School of Chemical Engineering, Sichuan University, Chengdu 610065, China.
Shandong Pharmaceutical Glass Co., Ltd., Zibo 256100, China.
ACS Omega. 2024 Jan 5;9(3):3499-3506. doi: 10.1021/acsomega.3c07194. eCollection 2024 Jan 23.
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.
随着基因治疗的不断发展，开发安全有效的阳离子聚合物载体至关重要。在这项工作中，基于肽-硫辛酸单体通过开环聚合制备了三种聚合物。通过调整肽的序列，获得了具有不同正电荷数的氧化还原响应型阳离子聚合物，并研究了它们作为基因载体的性能。结果表明，这些聚合物通过静电相互作用与带负电荷的基因复合，并成功地将基因转运到细胞中，此外在谷胱甘肽（GSH）条件下可降解并释放基因。此外，这些聚合物作为不同细胞系中的基因载体表现出较低的细胞毒性，在相同浓度下，其优异的细胞存活率比“金标准”聚乙烯亚胺（PEI）高8倍。体外转染实验表明，这些聚合物成功地将基因释放并转染到细胞中，证明了它们在基因治疗中的巨大潜力。
