Abstract
A successful siRNA delivery system is dependent on the development of a good siRNA carrier. Graphene oxide (GO) has gained great attention as a promising nanocarrier in recent years. It has been reported that GO could be used to deliver a series of drugs including synthetic compounds, proteins, antibodies, and genes. Our previous research indicated that functionalized GO could deliver siRNA into tumor cells and induce a gene silencing effect, to follow up the research, in this research, GO-R8/cRGDfV(GRcR) was designed and prepared for VEGF-siRNA delivery as a novel carrier. The Zeta potential and particle size of the new designed GRcR carrier was measured at (29.46 ± 5.32) mV and (135.7 ± 3.3) nm respectively, and after transfection, the VEGF mRNA level and protein expression level were down-regulated by 48.22% (p < 0.01) and 38.3% (p < 0.01) in HeLa cells, respectively. The fluorescent images of the treated BALB/c nude mice revealed that GRcR/VEGF-siRNA could conduct targeted delivery of VEGF-siRNA into tumor tissues and showed a gene silencing effect as well as a tumor growth inhibitory effect (p < 0.01) in vivo. Further studies showed that GRcR/VEGF-siRNA could effectively inhibit angiogenesis by suppressing VEGF expression. Histology and immunohistochemistry studies demonstrated that GRcR/VEGF-siRNA could inhibit tumor tissue growth effectively and have anti-angiogenesis activity, which was the result of VEGF protein downregulation. Both in vitro and in vivo results demonstrated that GRcR/VEGF-siRNA could be used as an ideal nonviral tumor-targeting vector for VEGF-siRNA delivery in gene therapy.
Highlights
RNA interference (RNAi) is a powerful approach and a promising technology used in gene therapy
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The results indicated that GRcR/VEGF-small interfering RNA (siRNA) could inhibit angiogenesis effectively by suppressing the expression and secretion of VEGF in HUVECs
Summary
RNA interference (RNAi) is a powerful approach and a promising technology used in gene therapy. It has been used to treat a variety of genetic diseases through inhibiting specific disease-causing gene function [1–4]. RNAi has been used in many therapeutic treatments, including clinical trials such as the treatment of age-related macular degeneration and respiratory syncytial virus [5]. Naked siRNA delivery is still limited due to these characters: poor water-solubility and high molecular weight [6–8]. Graphene oxide (GO) has gained attention due to its unique characteristics including good water dispensability, large surface area, and good biocompatibility. It has been used to design carriers
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