State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China.
Sci Rep. 2020 Feb 17;10(1):2717. doi: 10.1038/s41598-020-59624-w.
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.
由于具有高比表面积,氧化石墨烯及其纳米粒子在双重药物输送和联合化疗方面具有巨大的潜力。在此,我们开发了顺铂(Pt)和阿霉素(DOX)双重载药聚乙二醇化纳米氧化石墨烯(pGO),以在一个系统中促进联合化疗。在这项研究中,制备了纳米级的 pGO-Pt/DOX,其粒径约为 161.50nm,并通过动电位、原子力显微镜、TEM、Raman、UV-Vis 和 FTIR 分析进行了表征。通过引入 pGO 提高了 Pt 的药物输送效率,并且优化了 DOX:Pt:pGO 的最终重量比为 0.376:0.376:1。体外研究表明,pGO-Pt/DOX 纳米颗粒可以有效地递送到肿瘤细胞中,在其中它们诱导明显的细胞凋亡和坏死,并表现出比单一药物输送系统或游离药物更高的生长抑制作用。pGO-Pt/DOX 诱导的癌细胞凋亡和坏死率最高,为 18.6%,几乎是 pGO-Pt 或 pGO-DOX 组的两倍。在凋亡和坏死象限。体内数据证实,与游离药物相比,pGO-Pt/DOX 双重药物输送系统减轻了 Pt 和 DOX 对正常器官的毒性。肿瘤抑制数据、组织病理学观察和免疫组织化学染色证实,双重药物输送系统比游离药物具有更好的抗癌效果。这些结果清楚地表明,pGO-Pt/DOX 双重药物输送系统为癌症治疗中的联合药物输送提供了手段。