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载有替莫唑胺和橄榄苦苷或芦丁的聚乳酸核壳纳米纤维网通过控制释放抑制神经胶质瘤细胞。

Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release.

机构信息

Department of Medical Biology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey.

Faculty of Engineering and Natural Sciences, Department of Polymer Materials Engineering, Bursa Technical University, Bursa, Turkey.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 2):126722. doi: 10.1016/j.ijbiomac.2023.126722. Epub 2023 Sep 8.

Abstract

Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) core-shell nanofiber webs were encapsulated with OL (PLA), rutin (PLA), and TMZ (PLA) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core-shell structures with an average diameter between 133 ± 30.7-139 ± 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLA and PLA suppressed GB cell viability with a controlled release that increased over 120 h, while PLA caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nano-webs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.

摘要

胶质母细胞瘤(GB)易发生术后复发。因此,需要针对手术区域内的复发性 GB 细胞采取局部治疗方法。在这项研究中,我们使用橄榄苦苷(OL)、芦丁及其与替莫唑胺(TMZ)的组合,开发了一种针对 GB 细胞的基于纳米纤维的局部治疗方法。聚乳酸(PLA)核壳纳米纤维网通过静电纺丝工艺包封 OL(PLA)、芦丁(PLA)和 TMZ(PLA)。SEM 可视化形态,总浸没法确定 PLA 网的释放特性。实时细胞跟踪分析细胞生长、吖啶橙/碘化丙啶双重染色分析细胞活力、划痕愈合试验分析迁移能力、球体形成试验分析肿瘤球体侵袭性。所有聚合物纳米纤维网均具有核壳结构,平均直径为 133±30.7-139±20.5nm。所有 PLA 网均促进细胞凋亡,抑制细胞迁移和球体生长(p<0.0001)。PLA 和 PLA 以控制方式释放,超过 120 小时后释放增加,从而抑制 GB 细胞活力,而 PLA 则导致细胞迅速抑制(p<0.0001)。总的来说,我们的研究结果表明,核壳纳米网可能成为一种针对复发性 GB 细胞的 OL 和 TMZ 控释的新型有效治疗工具。

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