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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

Authors Wei Z, Yin XT, Cai Y, Xu WG, Song CH, Wang YF, Zhang JW, Kang A, Wang ZY, Han W

Received 14 November 2017

Accepted for publication 11 January 2018

Published 13 March 2018 Volume 2018:13 Pages 1505—1524

DOI https://doi.org/10.2147/IJN.S156984

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Farooq Shiekh

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang


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

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