Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma

Zheng Wei,1,2,* Xiteng Yin,1,2,* Yu Cai,2,3 Wenguang Xu,1,2 Chuanhui Song,1,2 Yufeng Wang,1,2 Jingwei Zhang,4 An Kang,5 Zhiyong Wang,1,2 Wei Han1,2 1Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 2Central Laborato...

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Autores principales:	Wei Z, Yin XT, Cai Y, Xu WG, Song CH, Wang YF, Zhang JW, Kang A, Wang ZY, Han W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Hypoxia tumor microenvironment Graphene oxide quantum dots Chemoresistance Pt-loaded nanocomplexes Oral squamous cell carcinoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0f3fab75f1194e52848112a4ed072ff6
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spelling	oai:doaj.org-article:0f3fab75f1194e52848112a4ed072ff62021-12-02T02:10:44ZAntitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma1178-2013https://doaj.org/article/0f3fab75f1194e52848112a4ed072ff62018-03-01T00:00:00Zhttps://www.dovepress.com/antitumor-effect-of-a-pt-loaded-nanocomposite-based-on-graphene-quantu-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Zheng Wei,1,2,* Xiteng Yin,1,2,* Yu Cai,2,3 Wenguang Xu,1,2 Chuanhui Song,1,2 Yufeng Wang,1,2 Jingwei Zhang,4 An Kang,5 Zhiyong Wang,1,2 Wei Han1,2 1Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 2Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 3Key Laboratory of Flexible Electronics and Institute of Advanced Materials, Jiangsu National Synergetic Innovation Center for Advanced Materials, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China; 4Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China; 5School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China *These authors contributed equally to this work Background: Tumor microenvironment plays an important role in the chemoresistance of oral squamous cell carcinoma (OSCC). Hypoxia in the microenvironment is one of the important factors that contributes to OSCC chemoresistance; therefore overcoming hypoxia-mediated chemoresistance is one of the great challenges in clinical practice. Methods: In this study, we developed a drug delivery system based on Pt-loaded, polyethylene glycol-modified graphene quantum dots via chemical oxidation and covalent reaction. Results: Our results show that synthesized polyethylene glycol-graphene quantum dots-Pt (GPt) is about 5 nm in diameter. GPt sensitizes OSCC cells to its treatment in both normoxia and hypoxia conditions. Inductively coupled plasma-mass spectrometry assay shows that GPt enhances Pt accumulation in cells, which leads to a notable increase of S phase cell cycle arrest and apoptosis of OSCC cells in both normoxia and hypoxic conditions. Finally, compared with free cisplatin, GPt exhibits a strong inhibitory effect on the tumor growth with less systemic drug toxicity in an OSCC xenograft mouse tumor model. Conclusion: Taken together, our results show that GPt demonstrates superiority in combating hypoxia-induced chemoresistance. It might serve as a novel strategy for future microenvironment-targeted cancer therapy. Keywords: hypoxia tumor microenvironment, graphene oxide quantum dots, chemoresistance, Pt-loaded nanocomplexes, oral squamous cell carcinomaWei ZYin XTCai YXu WGSong CHWang YFZhang JWKang AWang ZYHan WDove Medical PressarticleHypoxia tumor microenvironmentGraphene oxide quantum dotsChemoresistancePt-loaded nanocomplexesOral squamous cell carcinomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1505-1524 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hypoxia tumor microenvironment Graphene oxide quantum dots Chemoresistance Pt-loaded nanocomplexes Oral squamous cell carcinoma Medicine (General) R5-920
spellingShingle	Hypoxia tumor microenvironment Graphene oxide quantum dots Chemoresistance Pt-loaded nanocomplexes Oral squamous cell carcinoma Medicine (General) R5-920 Wei Z Yin XT Cai Y Xu WG Song CH Wang YF Zhang JW Kang A Wang ZY Han W Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma
description	Zheng Wei,1,2,* Xiteng Yin,1,2,* Yu Cai,2,3 Wenguang Xu,1,2 Chuanhui Song,1,2 Yufeng Wang,1,2 Jingwei Zhang,4 An Kang,5 Zhiyong Wang,1,2 Wei Han1,2 1Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 2Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China; 3Key Laboratory of Flexible Electronics and Institute of Advanced Materials, Jiangsu National Synergetic Innovation Center for Advanced Materials, School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing, China; 4Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China; 5School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China *These authors contributed equally to this work Background: Tumor microenvironment plays an important role in the chemoresistance of oral squamous cell carcinoma (OSCC). Hypoxia in the microenvironment is one of the important factors that contributes to OSCC chemoresistance; therefore overcoming hypoxia-mediated chemoresistance is one of the great challenges in clinical practice. Methods: In this study, we developed a drug delivery system based on Pt-loaded, polyethylene glycol-modified graphene quantum dots via chemical oxidation and covalent reaction. Results: Our results show that synthesized polyethylene glycol-graphene quantum dots-Pt (GPt) is about 5 nm in diameter. GPt sensitizes OSCC cells to its treatment in both normoxia and hypoxia conditions. Inductively coupled plasma-mass spectrometry assay shows that GPt enhances Pt accumulation in cells, which leads to a notable increase of S phase cell cycle arrest and apoptosis of OSCC cells in both normoxia and hypoxic conditions. Finally, compared with free cisplatin, GPt exhibits a strong inhibitory effect on the tumor growth with less systemic drug toxicity in an OSCC xenograft mouse tumor model. Conclusion: Taken together, our results show that GPt demonstrates superiority in combating hypoxia-induced chemoresistance. It might serve as a novel strategy for future microenvironment-targeted cancer therapy. Keywords: hypoxia tumor microenvironment, graphene oxide quantum dots, chemoresistance, Pt-loaded nanocomplexes, oral squamous cell carcinoma
format	article
author	Wei Z Yin XT Cai Y Xu WG Song CH Wang YF Zhang JW Kang A Wang ZY Han W
author_facet	Wei Z Yin XT Cai Y Xu WG Song CH Wang YF Zhang JW Kang A Wang ZY Han W
author_sort	Wei Z
title	Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma
title_short	Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma
title_full	Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma
title_fullStr	Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma
title_full_unstemmed	Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma
title_sort	antitumor effect of a pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/0f3fab75f1194e52848112a4ed072ff6
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Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma

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