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Iranian Journal of Basic Medical Sciences، جلد ۲۷، شماره ۱۲، صفحات ۱۶۰۴-۱۶۱۵
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عنوان انگلیسی Doxorubicin-loaded NK exosomes enable cytotoxicity against triple-negative breast cancer spheroids
چکیده انگلیسی مقاله Objective(s): Natural killer (NK) cells are the most professional innate immune cells that initiate extracellular apoptosis via cytotoxic granules in malignant cells. Antitumoral properties of NK-derived exosomes (Exos) are attributed to their parent cells. Loading drugs into Exos as a carrier can enhance their effect and enable targeted delivery. In the present study, we aim to deliver Doxorubicin (DOX) to the breast cancer spheroids by NK-Exos.Materials and Methods: Peripheral blood mononuclear cells (PBMC) were used to harvest NK cells, and NK-Exos were isolated from NK cell expansion medium using an Exo-spinTM kit. DOX was loaded via the ultrasonication method. AO/EtBr, Annexin/PI, DAPI, MTT, and spheroids of human breast cancer were used to track the cytotoxic effect of DOX-NK-Exos. The colony formation assay, scratch and transwell assays, Real-Time PCR for p53 and VEGF-A, and WB for protein expression were also performed.Results: When compared to free DOX, all viability tests validated the inhibitory effects of DOX-NK-Exos. The obtained results indicated that DOX-NK-Exos selectively reduced tumor cell viability and spared fibroblast and MCF-10A as noncancerous cells. Long after spheroid treatment, DOX-NK-Exos’ remarkable effect persisted.Conclusion: Human breast carcinoma mass treated with DOX-NK-Exos underwent apoptosis and showed a strong inhibitory effect on proliferation. Thus, they can reduce the side effects of chemotherapeutics and can be used as drug carriers with selective toxicity. Additionally, the additive action of this combination formula results in a more severe loss in cell viability.
کلیدواژه‌های انگلیسی مقاله Breast Cancer, Cellular spheroid, chemotherapy, Exosome, Natural killer cells
نویسندگان مقاله | Zahra Sadat Hashemi
ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran


| Mahlegha Ghavami
Pathology Department, Dalhousie University, Halifax, Canada


| Fateme Mohammadi
Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran


| Mahdieh Shokrollahi Barough
ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran


| Farhad Shokati
Biomaterials and Tissue Engineering Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran


| Saber Asghari
ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran


| saeed khalili
Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran


| Mandana Akbari Yekta
Biomaterials and Tissue Engineering Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran


| Ardeshir Ghavamzadeh
Cancer and Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran


| Ramin Sarrami Forooshani
ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
نشانی اینترنتی https://ijbms.mums.ac.ir/article_24757.html
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