GSH-Responsive GalNAc-Conjugated Glycopolymer for Targeted Survivin siRNA Delivery in Hepatocellular Carcinoma Therapy

Gene interference therapy has made significant progress in the treatment of various diseases by targeting specific pathogenic genes and down-regulating the production of harmful proteins. This approach enables the precise modulation of gene expression, offering potential therapeutic benefits for conditions driven by genetic mutations or abnormal protein accumulation. Survivin, an apoptosis-inhibiting protein, plays a critical role in regulating tumor cell proliferation and preventing programmed cell death. Its overexpression in liver cancer cells is strongly associated with poor prognosis and accelerated tumor progression. RNA interference (RNAi) therapy can effectively suppress the expression of Survivin in liver cancer, inhibiting tumor cell proliferation and promoting apoptosis. In this study, four distinct GalNAc-conjugated glycopolymer siRNA delivery systems were developed. By leveraging the efficient liver-targeting capability of the GalNAc moiety, Survivin-siRNA was specifically delivered to liver cancer cells through either covalent coupling or electrostatic adsorption. In vitro experiments demonstrated the excellent gene silencing effect of these siRNA complexes, highlighting their potential as a promising therapeutic strategy for liver cancer.