• Improved TRAIL Efficiency by Mitoxantrone loaded PLGA Nanoparticles in Glioblastoma Cancer Cell
  • Maryam Hashemi,1 Khalil Abnous,2 Soudabeh Balarastaghi,3 Narges Hedayati,4 Rezvan Yazdian‑Robati,5 Zahra Salmasi,6,*
    1. Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
    2. Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
    3. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
    4. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
    5. Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
    6. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran


  • Introduction: Glioblastoma (GBM) is one of the aggressive and lethal form of brain tumors, with a high degree of invasion. Drug resistance of tumor cells is one of important reasons that prevents the success of therapeutic strategies. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), is a type-II transmembrane protein belongs to the tumor necrosis factor (TNF) superfamily wich induces apoptosis in different tumor cells but not in most normal cells. Nevertheless, there are some limitation in TRAIL clinical application because of its short biological half-life and TRAIL resistance mechanisms. On the other hand, combination therapy is known as a possible solution for many drug resistances. Mitoxantrone (MTX) as an efficient anti-neoplastic drug has been prescribed against malignant glial cells and has been classified as a BCS-IV (low solubility/low permeability). Myelosuppression, neuropathy and nephrotoxicity have been reported as the important side effects of MTX. Therefore, a novel drug delivery system for MTX could be promising to reduce its adverse effects and fix the low solubility. So, in the current study, a system comprising of Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with MTX along with TRAIL plasmid delivery to glioblastoma cancer cells was designed and increase in their sensitivity was investigated.
  • Methods: PLGA nanoparticles containing MTX were fabricated using a water-in-oil-in-water (W/O/W) double emulsification and solvent evaporation method and characterized. Synergistic effect of PLGA-MTX and TRAIL plasmid delivery to cancer cells was evaluated by both MTT and annexin V-FITC/PI investigation against GL-261 cancer cell line.
  • Results: Significant more cytotoxic effect on GL-261 cells was acquired with combination treatment of PLGA-MTX nanoparticles and TRAIL plasmid, consequently cell viability of this treatment was 16% compared to 38% for MTX-PLGA alone and 87% for TRAIL alone treatments.
  • Conclusion: It concluded that PLGA-MTX can be remarked as a potential agent for sensitizing glioblastoma cancer cells to TRAIL. However, further studies are necessary for its clinical applications.
  • Keywords: Glioblastoma, TRAIL, Mitoxantrone · PLGA.