Small interfering RNA (siRNA) can be exploited to silence specific genes associated with cancer development, and successful siRNA therapy is highly dependent on the efficiency of the siRNA delivery vector. Herein, a well-designed novel redox- and enzyme-responsive fluorinated polyarginine (PFC-PR) was developed to be used as an anti-cancer siRNA carrier. The multiple guanidine groups could provide positive charges and bind with siRNA efficiently, and further fluorination modification enhanced the interaction with siRNA, resulting in a more stable PFC-PR/siRNA nanocomplex, improving serum tolerance, and promoting cellular uptake and endosome escape. Meanwhile, the PFC-PR was responsive to overexpressed cathepsin B and high levels of glutathione in cancer cells, conferring its ability to enhance siRNA release within cancer cells and making it cancer-targeting. Consequently, PFC-PR showed good biocompatibility and high gene silencing efficiency, which could inhibit cancer cell growth when delivered the siRNA targeting vascular endothelial growth factor, suggesting that it can be potentially used for anti-cancer gene therapy applications.

小干扰 RNA (siRNA) 可用于沉默与癌症发展相关的特定基因，成功的 siRNA 治疗高度依赖于 siRNA 递送载体的效率。在此，开发了一种精心设计的新型氧化还原和酶响应氟化聚精氨酸 (PFC-PR) 用作抗癌 siRNA 载体。多个胍基团可以提供正电荷并与siRNA有效结合，进一步的氟化修饰增强了与siRNA的相互作用，产生更稳定的PFC-PR/siRNA纳米复合物，提高血清耐受性，促进细胞摄取和内体逃逸。同时，PFC-PR 对癌细胞中过度表达的组织蛋白酶 B 和高水平的谷胱甘肽有反应，赋予其增强癌细胞内 siRNA 释放的能力，并使其成为癌症靶向。因此，PFC-PR 显示出良好的生物相容性和高基因沉默效率，当递送靶向血管内皮生长因子的 siRNA 时可以抑制癌细胞生长，表明它可以潜在地用于抗癌基因治疗应用。