Preparation and Characterization of Functionalized Graphene Oxide Carrier for siRNA Delivery.
Preparation and Characterization of Functionalized Graphene Oxide Carrier for siRNA Delivery.
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用于 siRNA 递送的功能化氧化石墨烯载体的制备和表征
DOI：
10.3390/ijms19103202
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发表时间：
2018-10-17
影响因子：
5.6
通讯作者：
Sun Q
中科院分区：
文献类型：
--
作者：
Li J;Ge X;Cui C;Zhang Y;Wang Y;Wang X;Sun Q
成功的siRNA递送系统依赖于良好的siRNA载体的开发。氧化石墨烯(GO)作为一种很有前途的纳米载体，近年来受到了极大的关注。据报道，GO可用于传递一系列药物，包括合成化合物、蛋白质、抗体和基因。我们以前的研究表明，功能化的GO可以将siRNA导入肿瘤细胞，并诱导基因沉默效应，为了进一步研究，本研究设计并制备了GO-R8/cRGDfV(GRcR)作为一种新型的血管内皮生长因子-siRNA载体。该载体的Zeta电位和颗粒大小分别为(2 9.46±5.32)mV和(135.7±3.3)nm，表达下调幅度分别为48.2 2%(P<0.0 1)和38.3%(P<0.0 1)。经治疗的BALB/c裸鼠的荧光图像显示，GRcR/VEGF-siRNA可将VEGF-siRNA靶向转移到肿瘤组织中，并在体内显示出基因沉默和肿瘤生长抑制作用(p<；0.01)。进一步研究表明，GRcR/VEGF-siRNA可通过抑制VEGF的表达而有效地抑制血管生成。组织学和免疫组织化学研究表明，GRcR/VEGF-siRNA能有效地抑制肿瘤组织的生长，并具有抗血管生成的活性，这是血管内皮生长因子蛋白下调的结果。体内外实验结果表明，GRcR/VEGF-siRNA可作为一种理想的非病毒肿瘤靶向载体应用于基因治疗。
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.
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