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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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Autores principales: Yin, Feng, Hu, Kuan, Chen, Yangzi, Yu, Mengying, Wang, Dongyuan, Wang, Qianqian, Yong, Ken-Tye, Lu, Fei, Liang, Yongye, Li, Zigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399581/
https://www.ncbi.nlm.nih.gov/pubmed/28435453
http://dx.doi.org/10.7150/thno.17841
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author Yin, Feng
Hu, Kuan
Chen, Yangzi
Yu, Mengying
Wang, Dongyuan
Wang, Qianqian
Yong, Ken-Tye
Lu, Fei
Liang, Yongye
Li, Zigang
author_facet 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
collection PubMed
description 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.
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spelling pubmed-53995812017-04-21 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 Theranostics Research Paper 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. Ivyspring International Publisher 2017-02-27 /pmc/articles/PMC5399581/ /pubmed/28435453 http://dx.doi.org/10.7150/thno.17841 Text en © 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.
spellingShingle Research Paper
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
title 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_short 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
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399581/
https://www.ncbi.nlm.nih.gov/pubmed/28435453
http://dx.doi.org/10.7150/thno.17841
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