Fabrication of poly(acrylic acid) grafted-chitosan/polyurethane/magnetic MIL-53 metal organic framework composite core-shell nanofibers for co-delivery of temozolomide and paclitaxel against glioblastoma cancer cells.

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-1) 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.