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PEGylated magnetic nanographene oxide for targeted delivery of arsenic trioxide and sec-o-glucosylhamaudol in tumor treatment with improved dual-drugs synergistic effect
AAPS Open Pub Date : 2023-06-05 , DOI: 10.1186/s41120-023-00079-4
Jinlai Cheng , Kun Hong , Jianhui Sun , Hongmei Li , Yu Zhao , Qinghe Zhao , Yuqing Tan , Miyi Yang

Arsenic trioxide (ATO) is a promising chemotherapeutic agent, but its clinical application is limited due to its poor pharmacokinetics and dose-limited toxicity. Moreover, the combination of ATO and sec-o-glucosylhamaudol (SOG) can improve the therapeutic effect of hepatoma. In this study, PEGylated magnetic nanographene oxide (PEG@MGO) was used as magnetic carriers to enhance the targeting ability of the drug delivery system. ATO and SOG are loaded on the surface of PEG@MGO nanoparticles through electrostatic interactions. This biocompatible nanocomposite shows magnetic susceptibility, pH sensitivity, and high loading capacity of the drugs. The in vitro cytotoxicity study of human hepatoma cell line (HepG2) cells showed more significant cytotoxicity and obvious synergistic effect between ATO and SOG compared with that of single drug-loaded nanoparticles via MTT assay. In vitro cellular uptake was observed by Prussian blue staining and fluorescently labeling. The results demonstrated a high cellular internalization rate of PEG@MGO. The ATO and SOG co-loaded nanodrug significantly inhibits the growth of tumors in vivo, which might be due to the oxidative stress and proapoptotic effect. This type of multidrug nanocomposite offers a promising alternative for cancer therapy. A pH-sensitive polyethylene glycol-modified magnetic graphene oxide loaded with ATO and SOG (PEG@MGO@ATO + SOG) was prepared for the magnetically targeted and efficient synergistic-chemo cancer therapy, which exhibited high specificity and good biocompatibility.

中文翻译:

聚乙二醇化磁性纳米氧化石墨烯用于肿瘤治疗中三氧化二砷和仲-o-葡糖基金缕梅的靶向递送,具有改善的双药协同效应

三氧化二砷(ATO)是一种很有前途的化疗药物,但由于其药代动力学差和剂量受限毒性,其临床应用受到限制。此外,ATO与sec-o-glucosylhamaudol (SOG)联合应用可提高肝癌的治疗效果。在这项研究中,聚乙二醇化磁性纳米氧化石墨烯(PEG@MGO)被用作磁性载体以增强药物递送系统的靶向能力。ATO 和 SOG 通过静电相互作用负载在 PEG@MGO 纳米粒子的表面。这种生物相容性纳米复合材料显示出磁敏感性、pH 敏感性和药物的高负载能力。人肝癌细胞系(HepG2)细胞的体外细胞毒性研究表明,与单一载药纳米粒子相比,ATO 和 SOG 具有更显着的细胞毒性和明显的协同作用。通过普鲁士蓝染色和荧光标记观察体外细胞摄取。结果表明 PEG@MGO 具有很高的细胞内化率。ATO 和 SOG 共同负载的纳米药物显着抑制体内肿瘤的生长,这可能是由于氧化应激和促凋亡作用。这种类型的多药纳米复合材料为癌症治疗提供了一种有前途的替代方案。制备了负载 ATO 和 SOG 的 pH 敏感聚乙二醇改性磁性氧化石墨烯 (PEG@MGO@ATO + SOG),用于磁性靶向和高效协同化疗癌症治疗,
更新日期:2023-06-05
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