Drug Design, Development and Therapy (Sep 2018)
Anti-HER2 functionalized graphene oxide as survivin-siRNA delivery carrier inhibits breast carcinoma growth in vitro and in vivo
Abstract
Xiaoli Wang,1–3 Qi Sun,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, Capital Medical University, Beijing, China; 3Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Capital Medical University, Beijing, China Background: The success of gene therapy is mostly dependent on the development of gene carrier. Graphene oxide (GO) possesses excellent aqueous solubility and biocompatibility, which is important for its biochemical and medical applications. Our previous work proved that GO can deliver siRNA into cells efficiently and downregulate the expression of desired protein.Methods: In this study, a novel delivery carrier, GO-R8/anti-HER2 (GRH), was developed by conjugating octaarginine (R8) and anti-HER2 antibody with GO as a tumor active-targeting vector for survivin-siRNA delivery.Results: GRH/survivin-siRNA formed nanoglobes of 195±10 nm in diameter. Real-time polymerase chain reaction analysis revealed that survivin messenger RNA expression showed a 42.4%±2.69% knockdown. The expression of survivin protein was downregulated to 50.86%±2.94% in enzyme-linked immunosorbent assay. In MTT tests, GRH exhibited no testable cytotoxicity. In vivo, GRH/survivin-siRNA showed gene silencing and inhibition of tumor growth.Conclusion: The in vitro and in vivo results consistently demonstrated that GRH/survivin-siRNA has potential to be an efficient gene silencing carrier for siRNA delivery in cancer therapy. Keywords: graphene oxide, GO, survivin-siRNA, anti-HER2 antibody, small interfering RNA, gene delivery, nanocarrier
