Glycyrrhetinic acid-modified graphene oxide mediated siRNA delivery for enhanced liver-cancer targeting therapy
| Autor: | Feng He, Chenggong Yu, Xiangna Zhang, Dong Liang, Ana Xu, Jun Wang, Feifei Sun, Jiahui Lv, Jingde Wu, Qiuqiong Zhang, Chen Yu, Ying Qu |
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| Rok vydání: | 2019 |
| Předmět: |
Vascular Endothelial Growth Factor A
Liver tumor Carcinoma Hepatocellular Cell Survival Genetic enhancement Pharmaceutical Science Mice Nude 02 engineering and technology 030226 pharmacology & pharmacy Polyethylene Glycols 03 medical and health sciences 0302 clinical medicine In vivo Dendrimer medicine Gene silencing Animals Humans Gene Silencing RNA Small Interfering Chemistry Liver Neoplasms Transfection Hep G2 Cells 021001 nanoscience & nanotechnology medicine.disease Gene Expression Regulation Neoplastic Cancer research Nanomedicine Glycyrrhetinic Acid Graphite 0210 nano-technology Liver cancer |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 139 |
| ISSN: | 1879-0720 |
| Popis: | 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 half-life, is a promising nanomedicine and may provide a new direction for highly-specific targeted gene therapy. |
| Databáze: | OpenAIRE |
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