Folate-targeted selenium nanoparticles deliver therapeutic siRNA to improve hepatocellular carcinoma therapy.

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 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 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 . 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.