纳米氧化石墨烯递呈阿霉素和抗 VEGF siRNA 协同治疗在体和离体肿瘤
Doxorubicin and anti-VEGF siRNA co-delivery via nano-graphene oxide for enhanced cancer therapy in vitro and in vivo.
机构信息
Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China,
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, China,
出版信息
Int J Nanomedicine. 2018 Jun 27;13:3713-3728. doi: 10.2147/IJN.S162939. eCollection 2018.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSION
The results indicated that co-delivery of siRNA and DOX by GPF could be a promising application in tumor clinical therapy.
背景
近年来，由于其独特的物理、化学和生物学特性，氧化石墨烯（GO）在生物和医学领域引起了广泛关注。在我们之前的工作中，已经证明 GO 可以将小干扰 RNA（siRNA）递送到细胞内，并下调所需基因的表达。
方法
本研究探讨了一种改良的 GO 纳米载体用于共递送 siRNA 和阿霉素（DOX）以增强癌症治疗的潜力。采用傅里叶变换红外光谱、激光粒度分析仪、紫外-可见光谱、凝胶电泳阻滞和体外释放试验进行了研究。
结果
实时聚合酶链反应的结果显示血管内皮生长因子（VEGF）mRNA 的表达降低了 46.84%±3.72%（均值±标准差）。酶联免疫吸附试验表明，VEGF 蛋白的表达在体外下调至 52.86%±1.10%（均值±标准差）。体内肿瘤生长试验结果表明，与裸 siRNA（1.62%±1.47%，均值±标准差）和 DOX（33.63%±5.85%，均值±标准差）相比，GO-聚-l-赖氨酸氢溴酸盐/叶酸（GPF）/DOX/siRNA 表现出基因沉默和肿瘤抑制（66.95%±2.35%，均值±标准差）。GPF/DOX/siRNA 无明显细胞毒性。
结论
结果表明，GPF 共递送 siRNA 和 DOX 可能是肿瘤临床治疗的一种有前途的应用。
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