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Abstract
Due to their high specific surface area, graphene oxide and graphene oxide-base nanoparticles have great potential both in dual-drug delivery and combination chemotherapy. Herein, we developed cisplatin (Pt) and doxorubicin (DOX) dual-drug-loaded PEGylated nano-graphene oxide (pGO) to facilitate combined chemotherapy in one system. In this study, nano-sized pGO-Pt/DOX ranged around 161.50 nm was fabricated and characterized using zeta-potential, AFM, TEM, Raman, UV-Vis, and FTIR analyses. The drug delivery efficacy of Pt was enhanced through the introduction of pGO, and the final weight ratio of DOX: Pt: pGO was optimized to 0.376: 0.376: 1. In vitro studies revealed that pGO-Pt/DOX nanoparticles could be effectively delivered into tumor cells, in which they induced prominent cell apoptosis and necrosis and exhibited higher growth inhibition than the single drug delivery system or free drugs. The pGO-Pt/DOX induced the most prominent cancer cell apoptosis and necrosis rate with 18.6%, which was observed almost 2 times higher than that of pGO-Pt or pGO-DOX groups. in the apoptosis and necrotic quadrants In vivo data confirmed that the pGO-Pt/DOX dual-drug delivery system attenuated the toxicity of Pt and DOX to normal organs compared to free drugs. The tumor inhibition data, histopathology observations, and immunohistochemical staining confirmed that the dual-drug delivery system presented a better anticancer effect than free drugs. These results clearly indicated that the pGO-Pt/DOX dual-drug delivery system provided the means for combination drug delivery in cancer treatment.
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1 Sichuan University, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Chengdu, China (GRID:grid.13291.38) (ISNI:0000 0001 0807 1581)