SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer
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. Graphe...
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sg-ntu-dr.10356-879662020-03-07T13:57:21Z SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer Yin, Feng Hu, Kuan Chen, Yangzi Yu, Mengying Wang, Dongyuan Wang, Qianqian Yong, Ken-Tye Lu, Fei Liang, Yongye Li, Zigang School of Electrical and Electronic Engineering Graphene Oxide (GO) SiRNA 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. Published version 2018-08-16T06:10:27Z 2019-12-06T16:53:07Z 2018-08-16T06:10:27Z 2019-12-06T16:53:07Z 2017 Journal Article Yin, F., Hu, K., Chen, Y., Yu, M., Wang, D., Wang, Q., et al. (2017). SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer. Theranostics, 7(5), 1133-1148. https://hdl.handle.net/10356/87966 http://hdl.handle.net/10220/45572 10.7150/thno.17841 en Theranostics © 2017 Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. 16 p. application/pdf |
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Graphene Oxide (GO) SiRNA |
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Graphene Oxide (GO) SiRNA Yin, Feng Hu, Kuan Chen, Yangzi Yu, Mengying Wang, Dongyuan Wang, Qianqian Yong, Ken-Tye Lu, Fei Liang, Yongye Li, Zigang SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer |
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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. |
author2 |
School of Electrical and Electronic Engineering |
author_facet |
School of Electrical and Electronic Engineering Yin, Feng Hu, Kuan Chen, Yangzi Yu, Mengying Wang, Dongyuan Wang, Qianqian Yong, Ken-Tye Lu, Fei Liang, Yongye Li, Zigang |
format |
Article |
author |
Yin, Feng Hu, Kuan Chen, Yangzi Yu, Mengying Wang, Dongyuan Wang, Qianqian Yong, Ken-Tye Lu, Fei Liang, Yongye Li, Zigang |
author_sort |
Yin, Feng |
title |
SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer |
title_short |
SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer |
title_full |
SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer |
title_fullStr |
SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer |
title_full_unstemmed |
SiRNA delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer |
title_sort |
sirna delivery with pegylated graphene oxide nanosheets for combined photothermal and genetherapy for pancreatic cancer |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/87966 http://hdl.handle.net/10220/45572 |
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1681046927993470976 |