Imatinib loaded in Exosomes derived frommesenchymal stem cells (MSC) as targeted therapy forChronic myeloid leukemia (CML)

Background: Exosomes (Exos) are a type of nano-sized extracellularvesicle, released from almost any type of cell andare characterized by a lipid bilayer membrane encapsulatingvarious bioactive molecules. As a natural carrier, Exos have theadvantages of low immunogenicity, high stability, and directdelivery of drugs to cells. Mesenchymal stem cells (MSCs) canmigrate to the tumor microenvironment so the MSC-derivedexosomes can also play a key role such as their parent cells.Indeed, drug loading into Exos as a carrier can synergies its effectand targeted delivery. Here, we considered the delivery ofImatinib to the K۵۶۲ cell line by MSC-derived exosomes.Materials and Methods: MSCs are obtained from abundantadipose tissue and Exos were isolated and characterized byDLS, TEM from MSC cell expansion media. Imatinib wasloaded via the ultrasonication method to obtain Imatinib-Exosformulation. The cytotoxic effects of Imatinib-Exos in K۵۶۲cells (CML cell line) were investigated by MTT. The Real-TimePCR of p۵۳ was performed for apoptosis pathway.Results: The positive expression of CD۹۰ and non-expressionof CD۴۵ for MSC were obtained. Particle size of Exos was analyzedusing DLS as ۱۸۷nm. The Exos' morphology as a saucer-like bilayer membrane structure was confirmed by TEM.The lethal IC۵۰ dose of Imatinib was ۳.۸μg/ml and all viabilityassays of Imatinib-Exos based on IC۵۰ dose established morethan ۲-fold inhibitory effects of Imatinib-Exos compared to thefree Imatinib.Conclusion: Imatinib-Exos showed a potent inhibitory effecton proliferation and induced apoptosis on K۵۶۲ cells. The resultdisplayed that Imatinib-Exos selectively reduced tumor cellviability, and the combined formula provided a synergistic effecton the reduction of cell viability. All data confirm that theycan be used as drug carriers with selective toxicity to the normalcells to reduce the side effects of chemotherapeutic drugs.

کلیدواژه ها:

Mesenchymal Stem Cells ، Exosomes ، Imatinib ، CML