Targeted delivery of HES5-siRNA with novel polypeptide-modified nanoparticles for hepatocellular carcinoma therapy

For actively targeted delivery of small interfering RNA (siRNA) to solid tumors, we fabricated functionalized selenium nanoparticles (SeNPs) decorated with the polypeptide RGDfC. Herein, RGDfC was used as tumor-targeted moiety and installed onto the surface of SeNPs to enhance the cellular uptake. RGDfC-SeNPs@siRNA were internalized into the HepG2 cell mainly through clathrin-mediated endocytosis. The active efficacy of the RGDfC-SeNPs@siRNA was confirmed via gene silencing assay, MTT assay and flow cytometry analysis. Owing to the tumor-targeting effect of RGDfC, RGDfC-SeNPs@siRNA achieved an obvious improvement in gene silencing ability, which led to significant growth inhibition of HepG2 cells. Furthermore, treatment with RGDfC-SeNPs@siRNA resulted in greater antitumor efficacy than lipofectamine 2000@siRNA in vitro and in vivo. In addition, the RGDfC-SeNPs@siRNA was almost non-toxic to the key organs of mice. In sum, these findings provide an alternative therapeutic route for targeted cancer treatments.