LAUSR

To obtain a tumor targeting siRNA delivery vehicle for hepatocellular carcinoma treatments, functionalized selenium nanoparticles, Se–PEI–FA, were first prepared by decorating selenium nanoparticles with polycationic polymers, polyethylenimine (PEI), linked with folic acid (FA). FA functions as the tumor-targeted molecule to enhance tumor targeting activity, and PEI conjugates FA and siRNA. Se–PEI–FA@siRNA entered HepG2 cells principally via clathrin-mediated endocytosis. Due to the active tumor targeting effectiveness of FA, Se–PEI–FA@siRNA has significantly higher cellular uptake and gene silencing efficiency, and more apparent cytotoxicity, in HepG2 cells compared with Se–PEI@siRNA. The silencing of HES5 by Se–PEI–FA@siRNA could induce HepG2 cells arrest at G0/G1 phase possibly via inhibiting protein expression of CDK2, cyclinE, and cyclinD1, and up-regulating the protein expression of p21. More importantly, Se–PEI–FA@siRNA exhibits more significant antitumor efficacy compared with Se–PEI@siRNA in vivo. Additionally, Se–PEI–FA@siRNA exhibits low toxicity to the important organs of tumor-bearing mice. This research provides an effective strategy for the design of tumor-targeted nanodrugs against hepatocellular carcinoma.