将奥利酚或芸香甙与替莫唑胺共载入聚乳酸核壳纳米纤维网中,通过控制释放抑制膠母细胞生长。
Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release.
发表日期:2023 Sep 04
作者:
Melis Ercelik, Cagla Tekin, Fatma Nur Parın, Busra Mutlu, Hazal Yılmaz Dogan, Gulcin Tezcan, Secil Ak Aksoy, Melisa Gurbuz, Kenan Yıldırım, Ahmet Bekar, Hasan Kocaeli, Mevlut Ozgur Taskapilioglu, Pınar Eser, Berrin Tunca
来源:
Int J Biol Macromol
摘要:
胶质母细胞瘤(GB)容易在手术后复发。因此,需要针对术后区域内的复发性GB细胞进行局部治疗。在本研究中,我们使用橄榄苷(OL)和芦丁以及它们与替莫唑胺(TMZ)的组合,开发了基于纳米纤维的局部治疗方法,针对GB细胞。通过电纺过程将聚乳酸(PLA)的核-壳纳米纤维网包裹于OL(PLAOL)、芦丁(PLArutin)和TMZ(PLATMZ)中。扫描电镜用于观察PLA纤维网的形态,全浸法确定其释放特性。采用实时细胞追踪分析细胞生长,采用双荧光染料曙红橙/碘化丙啶染色检测细胞活力,刮伤愈合实验评估细胞迁移能力,用球体形成实验评估肿瘤球体的侵袭性。所有聚合物纳米纤维网具有核-壳结构,平均直径在133±30.7-139±20.5nm之间。所有PLA纤维网均促进凋亡细胞死亡,抑制细胞迁移和球体生长(p < 0.0001)。PLAOL和PLATMZ通过控制释放,在120小时内抑制GB细胞的活力增加,而PLArutin导致快速的细胞抑制(p < 0.0001)。总的来说,我们的研究结果表明,核-壳纳米纤维网可以成为针对复发性GB细胞的橄榄苷和TMZ控制释放的新型有效治疗工具。版权©2023 Elsevier B.V.出版。
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 (PLAOL), rutin (PLArutin), and TMZ (PLATMZ) 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). PLAOL and PLATMZ suppressed GB cell viability with a controlled release that increased over 120 h, while PLArutin 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.Copyright © 2023. Published by Elsevier B.V.