International Journal of Nanomedicine (Jun 2018)
Doxorubicin and anti-VEGF siRNA co-delivery via nano-graphene oxide for enhanced cancer therapy in vitro and in vivo
Abstract
Qi Sun,1–3 Xiaoli Wang,1–3 Chunying Cui,1–3 Jing Li,1–3 Yifan Wang1–3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, China; 3Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, China 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 downregulated 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. Keywords: graphene oxide, siRNA delivery, co-delivery carrier, cervical carcinoma
