The importance of targeted miRNA deliveryof therapeutics using mesenchymal stem cells-derivedexosomes to cancer stem cells in the treatment of breast cancer

Breast cancer is considered one of the main causes of cancerassociateddeaths in women worldwide. Unfortunately, the incidenceof breast cancer is increasing, and current treatments areineffective for curing the majority of patients. In addition, manyside effects related to off-target effects of therapeutic drugs andimmune responses have been observed, which may result fromnon-specific targeting and less-than-optimal effectiveness ofdrugs. Therefore, the development of more efficient and precisetherapeutic factors by targeting the tumor microenvironmentand the underlying cancer progression mechanisms canadvance the field of breast cancer therapy. Breast cancer stemcells (BCSCs) are critical targets in the fight against cancer, asthese self-renewing tumorigenic cell compartments are thoughtto be responsible for metastasis and tumor recurrence. Thecombination of miRNAs and chemotherapy agents might havesignificant effects on the survival, proliferation, and invasionof resistant CSCs. However, miRNA therapy has the risk ofoff-target effects that can lead to unpredictable phenotypes. Accordingly,active targeting, especially through exosomes, wouldbe a promising way to solve this problem. In order to isolatemore applicable exosomes for delivery of miRNAs, differentcell sources have been examined; among them, umbilical cordderivedmesenchymal stem cells (MSCs) exhibited anti-tumorproperties and a great tendency to move towards tumor cells,which highlighted them as appropriate cell sources for exosomeisolation. As a result, MSCs-derived exosomes, by encapsulatingthe drugs and other therapeutic factors, and increasing thehalf-life and stability of the cargos, can be used as promisingnanocarriers for the targeted delivery of therapeutics to specifictissues. In the present review, we will provide an overview ofCSCs, their role in cancer progression and chemoresistance, the main findings of the effects of miRNA and on CSCs. Furthermore,we will discuss the role of engineered exosomes as a vehiclein CSCs appropriate targeting

کلیدواژه ها:

Cancer Stem Cells ، miRNA ، Targeted therapy ، Exosomes