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Targeted Delivery of siRNA to Ovarian Cancer Cells Using Functionalized Graphene Oxide

Tianjin Polytechnic University, No. 399 Binshui Road, Xiqing District, Tianjin, P. R. China

The Affiliated Hospital of Jining Medical University, No. 89, Guhuai Road, Jining, Shandong, P. R. China

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xietu Road, Shanghai, P. R. China

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Kai Wang

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xietu Road, Shanghai, P. R. China

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Zhiying Zhang

Tianjin Polytechnic University, No. 399 Binshui Road, Xiqing District, Tianjin, P. R. China

E-mail Address: z.zhang@tjpu.edu.cn

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Linqing Yang

The Affiliated Hospital of Jining Medical University, No. 89, Guhuai Road, Jining, Shandong, P. R. China

E-mail Address: Linqingyang1991@163.com

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, and

Xiaofei Liang

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, No. 25, Lane 2200, Xietu Road, Shanghai, P. R. China

E-mail Address: xfliang@shsci.org

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https://doi.org/10.1142/S1793984418500010Cited by:5 (Source: Crossref)

Abstract

Ovarian cancer is the highest mortality rate of all cancers in the female reproductive system. Over the past decades, small interfering RNA (si RNA) has been explored as a promising therapeutic candidate for gene therapy. However, its clinical application is limited by the lack of safe and efficient methods for gene delivery. Graphene oxide (GO) was modified with polyethylene glycol (PEG), polyethylenimine (PEI) and folic acid (FA), for targeted delivery of small interfering RNA (siRNA) that inhibits ovarian cancer cell growth, and the efficacy of such complex was evaluated by a series of in vitro experiments. The synthesized vehicle PEG-GO-PEI-FA was characterized by atomic force microscopy (AFM), Malvern particle size analyzer, UV-visible spectroscopy and Fourier transform infrared spectroscopy (FTIR), and the results showed that PEG, PEI and FA could be covalently grafted to GO surface, forming PEG-GO-PEI-FA particles with a size of $216.1 \pm 2.457$ nm and a potential of 14.7mV. Agarose-gel electrophoresis demonstrated that siRNA can be adsorbed onto the surface of PEG-GO-PEI-FA by electrostatic interaction. Laser confocal microscopy demonstrated that siRNA-adsorbed PEG-GO-PEI-FA could be target into folate receptor (FR)-overexpressing ovarian cancer cells. Compared to the PEG-GO-PEI/siRNA without folate modification, PEG-GO-PEI-FA/siRNA showed more pronounced inhibitory effect on growth of ovarian cancer cells. In conclusion, we have successfully synthesized a vector that is safe, efficient and specific to target tumor cell for gene delivery.

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