Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 139, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejps.2019.105036
Keywords
Graphene oxide; siRNA; Glycyrrhetinic acid; Active targeting; Anti-liver cancer
Categories
Funding
- Fundamental Research Fund of Shandong University [2016JC025]
- Key Research and Development Program of Shandong Province [2017CXGC1401]
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Graphene oxide (GO) has attracted huge attention in biomedical field in recent years. However, limited attempts have been invested in utilizing GO on active targeted delivery for gene therapy in liver cancer treatments. Glycyrrhetinic acid (GA) has been reported to be widely used as a targeting ligand to functionalize nanomaterials to treat hepatocellular carcinoma. In this article, GA is employed as a liver targeting ligand to construct GA, polyethylene glycol (PEG), polyamidoamine dendrimer (Dendrimer) and nano-graphene oxide (NGO) conjugate (GA-PEG-NGO-Dendrimer, GPND) for siRNA delivery for the first time. As we expected, GPND exhibited excellent stability, low toxicity, negligible hemolytic activity and remarkably high transfection efficiency in vitro. We also found effective VEGFa gene silencing in both mRNA and protein level in HepG2 cells. Notably, siRNA efficiently gathered in liver tumor tissues by the delivery of GPND, and eventually the growth of tumor tissues were inhibited with enhanced targeting capability and no obvious pathological changes. Moreover, histopathological results preliminarily support the high in vivo safety of GPND/anti-VEGFa siRNA nanocomplex. Collectively, GPND/siRNA nanocomplex, with high safety, targeting and transfection as well as prolonged halflife, is a promising nanomedicine and may provide a new direction for highly-specific targeted gene therapy.
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