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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

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 grea...

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Detalles Bibliográficos
Autores principales: Wei, Zheng, Yin, Xiteng, Cai, Yu, Xu, Wenguang, Song, Chuanhui, Wang, Yufeng, Zhang, Jingwei, Kang, An, Wang, Zhiyong, Han, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856292/
https://www.ncbi.nlm.nih.gov/pubmed/29559779
http://dx.doi.org/10.2147/IJN.S156984
Descripción
Sumario: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.