Synthesis of KUE-siRNA Conjugates for Prostate Cancer Cell-Targeted Gene Silencing.
2021
The delivery of siRNAs to selectively target cells poses a great challenge in RNAi-based cancer therapy. The lack of suitable cell-targeting methods seriously restricts the advance in delivering siRNAs to extrahepatic tissues. Based on prostate-specific membrane antigen (PSMA)-targeting ligands, we have synthesized a series of lysine-urea-glutamate (KUE)-siRNA conjugates and verified their effective cell uptake and gene silencing properties in prostate cancers. The results indicated that the KUE-siRNA conjugates could selectively enter PSMA+ LNCaP cells, eventually down-regulating STAT3 expression. Based on post-synthesis modification and receptor-mediated endocytosis, this strategy of constructing ligand-siRNA conjugates might provide a general method of siRNA delivery for cell-targeted gene silencing.
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