Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, North Cyprus via Mersin 10, Turkey.
Department of Chemical Engineering, Sciences and Research Branch, Islamic Azad University, Tehran, Iran.
Int J Pharm. 2020 Sep 25;587:119674. doi: 10.1016/j.ijpharm.2020.119674. Epub 2020 Jul 21.
In the present study, the magnetic MIL-53 nanometal organic framework particles (NMOFs) were incorporated into poly(acrylic acid) grafted-chitosan/polyurethane (PA-g-CS/PU) core-shell nanofibers for controlled release of temozolomide (TMZ) and paclitaxel (PTX) against U-87 MG glioblastoma cells during chemotherapy/hyperthermia combined method. The synthesized magnetic MIL-53 NMOFs and NMOF-loaded nanofibers were characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), Fourier transformed infrared (FTIR), vibrating-sample magnetometer (VSM) and scanning electron microscopy (SEM) analysis. The TMZ and PTX release profiles from magnetic MIL-53 5 wt% loaded-CS-g-PAA-PTX-TMZ/PU fibers were investigated under acidic and physiological pH at temperatures of 37 and 43 °C. The effect of hyperthermia on the release rate of TMZ and PTX from magnetic nanofibers was investigated. An alternating magnetic field could induce the mild hyperthermia (43 °C) for the cells treated with magnetic MIL-53 5 wt% loaded-CS-g-PAA-PTX-TMZ/PU fibers during 10 min. The release data were best described by the non-Fickian diffusion of Korsmeyer-Peppas equation. The cell viability, flowcytometry and Bcl-2, Bax expression levels were investigated to obtain the optimum nanofibrous carrier for apoptosis of U-87 MG cells in vitro. The obtained results indicated that the synthesized magnetic MIL-53 NMOFs loaded- PA-g-CS/PU/TMZ-PTX nanofibers (shell flow rate: 0.8 mLh) could be used as a targeted delivery of anticancer agents with maximum apoptosis of 49.6% of U-87 MG glioblastoma cells under AMF during chemotherapy/hyperthermia combination therapy.
在本研究中，将磁性 MIL-53 纳米金属有机骨架颗粒（NMOFs）掺入聚（丙烯酸）接枝壳聚糖/聚氨酯（PA-g-CS/PU）核壳纳米纤维中，用于在化疗/高温联合治疗期间控制替莫唑胺（TMZ）和紫杉醇（PTX）的释放，以对抗 U-87 MG 神经胶质瘤细胞。使用 X 射线衍射（XRD）、BET、傅里叶变换红外（FTIR）、振动样品磁强计（VSM）和扫描电子显微镜（SEM）分析对合成的磁性 MIL-53 NMOFs 和负载 NMOF 的纳米纤维进行了表征。在 37 和 43°C 的酸性和生理 pH 下，研究了载有 5wt%磁性 MIL-53 的 CS-g-PAA-PTX-TMZ/PU 纤维中 TMZ 和 PTX 的释放曲线。研究了高温对磁性纳米纤维中 TMZ 和 PTX 释放速率的影响。交变磁场可以在 10 分钟内诱导经磁性 MIL-53 5wt%负载 CS-g-PAA-PTX-TMZ/PU 纤维处理的细胞产生温和的高温（43°C）。释放数据通过 Korsmeyer-Peppas 方程的非 Fickian 扩散得到最好的描述。为了获得体外 U-87 MG 细胞凋亡的最佳纳米纤维载体，研究了细胞活力、流式细胞术和 Bcl-2、Bax 表达水平。结果表明，合成的载有磁性 MIL-53 NMOFs 的 PA-g-CS/PU/TMZ-PTX 纳米纤维（壳层流速：0.8 mLh）可作为抗癌药物的靶向递送系统，在化疗/高温联合治疗期间，交变磁场可使 U-87 MG 神经胶质瘤细胞的凋亡率达到 49.6%。
