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Int J Pharm. 2019 Mar 10;558:441. doi: 10.1016/j.ijpharm.2019.02.003.

Corrigendum to "Exosomes derived from TRAIL-engineered mesenchymal stem cells with effective anti-tumor activity in a mouse melanoma model" [International Journal of Pharmaceutics 549 (2018) 218-229].

Author information

1
Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2
Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran.
3
Nanotechnology research center, Pharmaceutical technology institute, Mashhad University of Medical Sciences, Mashhad, Iran.
4
Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
5
Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
6
Department of Pathology, Faculty of Medicine, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
7
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Ramezanim@mums.ac.ir.
8
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Abnouskh@mums.ac.ir.

Abstract

Exosomes are biological nano-sized vesicles (~30-200 nm in diameter) that are produced by a wide range of cells and play several roles in cell-cell communications. These vesicles contain membrane and cytoplasmic components of producing cells. Mesenchymal stem cells (MSCs) are the ideal producer of exosomes. The secreted vesicles from MSCs are promising biological vehicles for cell-free therapy in regenerative medicine, cancer therapy and targeted delivery of therapeutic agents to the tumor cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising member of the TNF family with selective effect on cancerous cells. Recent evidences showed that the membrane TRAIL-armed exosomes possess anti-tumor activity. However, the effect of in vivo administration of TRAIL-armed exosomes has not been reported so far. In the current study, mesenchymal stem cells expressing TRAIL/GFP proteins were prepared with the help of a non-viral vector based on polyethylenimine 25 kDa. Then, exosomes containing TRAIL protein (Exo-TRAIL) were isolated from the supernatant of genetically engineered MSCs and characterized. Antitumor activity of both MSC-derived exosomes and Exo-TRAIL was investigated in vitro and in vivo in three models. The results indicated that the co-injection of both Exo-TRAIL and tumor cells delayed the tumor appearance. Besides, the tumor volume/weight was efficiently decreased in tumor bearing mice. Moreover, it was shown that multi-dose injections of Exo-TRAIL reduced the tumor size while single dose treatment with Exo-TRAIL did not show significant anti-tumor activity. To conclude, these results suggested that MSC-derived Exo-TRAIL has a potential capacity for cancer treatment.

KEYWORDS:

Cancer; Exo-TRAIL; Exosome; Mesenchymal stem cells; TRAIL

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