Doxorubicin and anti-VEGF siRNA co-delivery via nano-graphene oxide for enhanced cancer therapy in vitro and in vivo.
Doxorubicin and anti-VEGF siRNA co-delivery via nano-graphene oxide for enhanced cancer therapy in vitro and in vivo.
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DOI：
10.2147/ijn.s162939
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发表时间：
2018
影响因子：
8
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Sun Q;Wang X;Cui C;Li J;Wang Y
氧化石墨烯（GO）由于其独特的物理、化学和生物学性质，近年来在生物和医学领域引起了广泛的兴趣。在我们之前的工作中，我们证明了GO可以将小干扰RNA（siRNA）递送到细胞中并下调所需基因的表达。本研究调查了修饰的GO纳米载体用于共同递送siRNA和多柔比星（DOX）以增强癌症治疗的潜力。采用红外光谱法、激光粒度分析仪、紫外-可见分光光度法、凝胶电泳阻滞法和体外释放度测定法进行了研究。实时荧光定量聚合酶链反应（PCR）检测结果显示，血管内皮生长因子（VEGF）mRNA表达降低46.84%±3.72%（mean ± SD）。酶联免疫吸附试验显示，体外培养的细胞VEGF蛋白表达下调至52.86%±1.10%（mean ± SD）。在体内肿瘤生长试验中，GO-多聚赖氨酸氢溴酸盐/叶酸（GPF）/DOX/siRNA与裸siRNA（1.62%± 1.47%，平均值± SD）和DOX（33.63%± 5.85%，平均值± SD）相比显示基因沉默和肿瘤抑制（66.95%± 2.35%，平均值± SD）。GPF/DOX/siRNA没有表现出可检测的细胞毒性。结果表明，GPF介导的siRNA和DOX共递送在肿瘤治疗中具有广阔的应用前景。
Graphene oxide (GO) has attracted intensive interest in biological and medical fields in recent years due to its unique physical, chemical, and biological properties. In our previous work, we proved that GO could deliver small interfering RNA (siRNA) into cells and downregulate the expression of the desired gene. This study investigated the potential of a modified GO nanocarrier for co-delivery of siRNA and doxorubicin (DOX) for enhanced cancer therapy. Fourier transform infrared spectroscopy, laser particle size analyzer, UV-visible spectroscopy, gel electrophoresis retardation, and in vitro release assay were studied. The results of real-time polymerase chain reaction revealed that the expression of vascular endothelial growth factor (VEGF) mRNA was decreased 46.84%±3.72% (mean ± SD). Enzyme-linked immunosorbent assay indicated that the expression of VEGF protein was down-regulated to 52.86%±1.10% (mean ± SD) in vitro. In vivo tumor growth assay GO-poly-l-lysine hydrobromide/folic acid (GPF)/DOX/siRNA exhibited gene silencing and tumor inhibition (66.95%±2.35%, mean ± SD) compared with naked siRNA (1.62%±1.47%, mean ± SD) and DOX (33.63%±5.85%, mean ± SD). GPF/DOX/siRNA exhibited no testable cytotoxicity. The results indicated that co-delivery of siRNA and DOX by GPF could be a promising application in tumor clinical therapy.