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Theranostics 2017; 7(5):1133-1148. doi:10.7150/thno.17841 This issue Cite

Research Paper

SiRNA Delivery with PEGylated Graphene Oxide Nanosheets for Combined Photothermal and Genetherapy for Pancreatic Cancer

Feng Yin^1*, Kuan Hu^1*, Yangzi Chen¹, Mengying Yu¹, Dongyuan Wang¹, Qianqian Wang¹, Ken-Tye Yong², Fei Lu^1✉, Yongye Liang^3✉, Zigang Li^1✉

1. School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China;
2. School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798, Singapore;
3. Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen, 518055, China.
* These authors contributed equally to this work.

✉ Corresponding authors: Zigang Li, email: lizgedu.cn; Fei Lu, email: lufeiedu.cn; Yongye Liang, email: liangyyedu.cn.

Abstract

Since the successful exfoliation of graphene from graphite in 2004, graphene and graphene oxide (GO) have been considered the most promising two-dimensional (2D) nanomaterials with distinguished physical and chemical characteristics and have attracted great attention in many different fields. Graphene oxide is well-known for its distinct physiochemical properties and shows only minimal cytotoxicity compared to carbon nanotubes. Until now, only limited efforts have been invested in utilizing GO for gene therapy in pancreatic cancer treatments. In this study, we utilized multi-functionalized monolayer GO as a gene delivery system to efficiently co-deliver HDAC1 and K-Ras siRNAs (small interfering RNAs targeting the HDAC1 gene and the G12C mutant K-Ras gene, respectively) to specifically target pancreatic cancer cells MIA PaCa-2. The systematic mechanistic elucidation of the dual gene silencing effects indicated the inactivation of both the HDAC1 and the K-Ras gene, thereby causing apoptosis, proliferation inhibition and cell cycle arrest in treated MIA PaCa-2 cells. The synergistic combination of gene silencing and NIR light thermotherapy showed significant anticancer efficacy, inhibiting in vivo tumor volume growth by >80%. Furthermore, GO can be metabolized in the mouse model within a reasonable period of time without obvious side effects. Based on preliminary in vivo application, this study for the first time indicates the promising potential of functionalized GO as a vehicle for gene therapy delivery with low toxicity for the treatment of pancreatic adenocarcinoma.

Keywords: Graphene Oxide (GO), siRNA, HDAC1, K-Ras, Folic acid (FA), Pancreatic cancer.

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