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

Abstract

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/hy-perthermia 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 degrees 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 degrees 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.