International Journal of Nanomedicine (Mar 2018)
Superparamagnetic iron oxide nanoparticles modified with polyethylenimine and galactose for siRNA targeted delivery in hepatocellular carcinoma therapy
Abstract
Zhen Yang,1,* Juanli Duan,1,* Jianlin Wang,1,* Qi Liu,1 Runze Shang,1 Xisheng Yang,1 Peng Lu,2 Congcong Xia,1 Lin Wang,1 Kefeng Dou1 1Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hainan Branch of Chinese PLA General Hospital, Sanya, People’s Republic of China *These authors contributed equally to this work Introduction: A safe and effective in vivo siRNA delivery system is a prerequisite for liver tumor treatment based on siRNA cancer therapeutics. Nanoparticles based on superparamagnetic iron oxide (SPIO) provide a promising delivery system. In this study, we aimed to explore a novel nanoparticle, which is composed of SPIO.Materials and methods: The particles have a core of iron oxide that is modified by galactose (Gal) and polyethylenimine (PEI), which act as shells, providing targeted delivery of therapeutic siRNA to the liver cancer. Gal-PEI-SPIO nanoparticles were synthesized, and the characteristics of the Gal-PEI-SPIO encapsulated with siRNA were analyzed.Results: The particles remained nanoparticles and displayed negligible cytotoxicity when loaded with siRNA. In a serum stability assay, the Gal-PEI-SPIO nanoparticles could shield the siRNA from serum degradation and prolong the half-life of the siRNA in the system. Simultaneously, we found that the mixture could be efficiently taken up by Hepa1–6 cells in a flow cytometry assay. To study the anticancer effect, quantitative polymerase chain reaction and Western blotting were used to validate the silencing efficacy of the complexes in vitro. Subsequently, the nanoparticle mixtures were administered intravenously to tumor-bearing mice to explore the tissue distribution and the effect of the siRNA against cancer. We found that the nanoparticles could provide targeted siRNA delivery, accumulate easily in orthotopic tumors, enhance siRNA accumulation in the tumor tissues for 24 h and protect the siRNA from serum nuclease degradation in comparison with the control group. After these study procedures, the mice were sacrificed, and the tumors were removed to compare the tumor size and analyze the therapeutic effect on tumor growth. The tumor volume and the liver/body weight ratio were significantly reduced in the si-c-Met therapy groups. Additionally, the mRNA levels were also lower than those observed in the controls.Conclusion: Based on these results, we concluded that Gal-PEI-SPIO represents a promising and efficient platform for siRNA delivery in tumor therapy. Keywords: Gal-PEI-SPIO, hepatocellular carcinoma, c-Met, nanoparticle, siRNA
