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Genistein and Temozolomide-Loaded Polymeric Nanoparticles: A Synergistic Approach For Improved Anti-Tumor Efficacy Against Glioblastoma
Process Biochemistry ( IF 3.7 ) Pub Date : 2021-07-16 , DOI: 10.1016/j.procbio.2021.07.015
Irem Meteoglu 1 , Aysegul Erdemir 1
Affiliation  

Glioblastoma multiforme (GBM) is one of the most malignant type of brain cancer. Highly invasive nature of GBM and poor drug penetration from physiological barriers makes GBM treatment challenging. In this study, temozolomide (TMZ) and genistein (Gen) dual-drug-loaded poly(lactic-co-glycolic-acid) nanoparticle systems (Gen-TMZ-NPs) were developed to achieve enhanced anti-tumor activity in U87MG human glioblastoma cells. For this aim, Gen-TMZ-NPs alongside TMZ and Gen single-drug-loaded PLGA-NPs were produced and physico-chemical properties of fabricated nanoparticles were examined by polydispersity index, mean particle size, zeta potential and FT-IR spectroscopy. In vitro cytotoxic activity of Gen-NP, TMZ-NP and Gen-TMZ-NPs on U87MG cells were assessed and an increased cytotoxicity was observed in Gen-TMZ-NP treated U87MG cells, with IC50 values 35.2 μg/ml for 24 h and 8.7 μg/ml for 48 h. U87MG cell migration activity was significantly inhibited in Gen-TMZ-NP treated group with 6.80% wound closure rate after 48 h treatment and BrdU incorporation assay established a decreased cell proliferation. Moreover, quantitative real-time PCR analysis and western blotting confirmed cytochrome-c mediated activation of apoptosis in Gen-TMZ-NP treated U87MG cells. Our results showed that Gen-TMZ-NPs exhibited improved anti-tumor activity in U87MG cells and that dual nano drug delivery might be a promising strategy against glioblastoma.



中文翻译:

染料木黄酮和替莫唑胺负载的聚合物纳米颗粒:一种提高对胶质母细胞瘤的抗肿瘤功效的协同方法

多形性胶质母细胞瘤(GBM)是恶性程度最高的脑癌之一。GBM 的高侵袭性和生理障碍的药物渗透性差使 GBM 治疗具有挑战性。在这项研究中,开发了替莫唑胺 (TMZ) 和染料木黄酮 (Gen) 双载药聚(乳酸-共-乙醇酸)纳米颗粒系统 (Gen-TMZ-NPs) 以增强 U87MG 人胶质母细胞瘤的抗肿瘤活性细胞。为此,生产了 Gen-TMZ-NP 以及 TMZ 和 Gen 单药负载 PLGA-NP,并通过多分散指数、平均粒径、zeta 电位和 FT-IR 光谱检查了制备的纳米颗粒的理化性质。评估了 Gen-NP、TMZ-NP 和 Gen-TMZ-NPs 对 U87MG 细胞的体外细胞毒活性,在 Gen-TMZ-NP 处理的 U87MG 细胞中观察到细胞毒性增加,IC50 个值 35.2 μg/ml 24 小时和 8.7 μg/ml 48 小时。U87MG 细胞迁移活性在 Gen-TMZ-NP 治疗组中被显着抑制,治疗 48 小时后伤口闭合率为 6.80%,BrdU 掺入试验确定细胞增殖降低。此外,定量实时 PCR 分析和蛋白质印迹证实细胞色素-c 介导了 Gen-TMZ-NP 处理的 U87MG 细胞中的细胞凋亡激活。我们的结果表明,Gen-TMZ-NPs 在 U87MG 细胞中表现出改善的抗肿瘤活性,双纳米药物递送可能是一种有前途的对抗胶质母细胞瘤的策略。

更新日期:2021-07-22
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