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

Abstract

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.

Synthesis of graphene quantum dots and their applications in drug delivery

“…To overcome the hypoxia-induced resistance to chemotherapy in the tumor microenvironment, Wei et al [189] established a DDRS based on Pt and polyethylene glycol-GQDs. First, GQDs were synthesized by chemical oxidation of dried CX-7 carbon black with HNO 3 .…”

“…13 Schematic illustration of a multifunctional platform for anticancer therapy with high efficacy against hypoxia-induced chemoresistance of OSCC (reprinted/reproduced with the permission of Ref. [ 189 ], (reprinted/reproduced with the permission of Ref. [ 189 ], copyright 2018, Int J Nanomedicine) …”

“…[ 189 ], (reprinted/reproduced with the permission of Ref. [ 189 ], copyright 2018, Int J Nanomedicine) …”

“… (reprinted/reproduced with the permission of Ref. [ 189 ], (reprinted/reproduced with the permission of Ref. [ 189 ], copyright 2018, Int J Nanomedicine) …”

A Comprehensive Review on the Synthesis, Characterization, and Biomedical Application of Platinum Nanoparticles

“…PtNPs induced apoptosis in Raw 264.7 cells by altering cell morphology and density and also increased apoptosis, activation of caspases 3 and 7, and DNA fragmentation [216]. Wei et al [217] reported that polyethylene glycol-graphene quantum dots-Pt (GPt) with an average size of 5 nm sensitize oral squamous cell carcinoma (OSCC) in both normoxic and hypoxic conditions. GPt exhibits a strong inhibitory effect on tumor growth with less systemic drug toxicity and helps in combating hypoxia-induced chemoresistance in an OSCC xenograft mouse tumor model.…”