Superparamagnetic iron oxide nanoparticles modified with polyethylenimine and galactose for siRNA targeted delivery in hepatocellular carcinoma therapy

Abstract

IntroductionA 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 methodsThe 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.ResultsThe 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.ConclusionBased on these results, we concluded that Gal-PEI-SPIO represents a promising and efficient platform for siRNA delivery in tumor therapy.

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Modification of SPION nanocarriers for siRNA delivery: A therapeutic strategy against HIV infection

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Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

“…This trend may be attributed to the solid structure of the constructs, which leads to formulations in which the siRNA payloads are covalently bound or chemically adhered to the surface of the particles (e.g., thiol‐gold chemistry) . This surface‐loading mechanism leaves the siRNA molecules exposed to the degrading conditions of the in vivo environment during circulation, which underscores the necessity for an siRNA‐protective design; thus, metallic systems generally employ cationic polymer/lipid coatings to facilitate loading and protection of the siRNA payload …”