Novel delivery of sorafenib by natural killer cell-derived exosomes-enhanced apoptosis in triple-negative breast cancer

Author:

Hashemi Zahra Sadat1ORCID,Ghavami Mahlegha2,Kiaie Seyed Hossein34,Mohammadi Fateme5,Barough Mahdieh Shokrollahi1,Khalili Saeed6ORCID,Hosseini-Farjam Zahra1,Mossahebi-Mohammadi Majid7,Sheidary Alireza8,Ghavamzadeh Ardeshir9,Forooshani Ramin Sarrami1ORCID

Affiliation:

1. ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, 15179/64311, Iran

2. Pathology Department, Dalhousie University, Halifax, B3H 4R2, Canada

3. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, 5166614711, Iran

4. Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, 6715847141, Iran

5. Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, 1417653761, Iran

6. Department of Biology Sciences, Shahid Rajaee Teacher Training University, Tehran, 167815811, Iran

7. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325027, China

8. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417653761, Iran

9. Cancer & Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, 1417653761, Iran

Abstract

Aim: We investigated the delivery of sorafenib (SFB) to breast cancer spheroids by natural killer cell-derived exosomes (NK-Exos). Methods: SFB-NK-Exos were constructed by electroporation. Their antitumor effects were evaluated by methyl thiazolyl tetrazolium, acridine orange/ethidium bromide, 4′,6-diamidino-2-phenylindole, annexin/propidium iodide, scratch and migration assay, colony formation, RT-PCR, western blot and lipophagy tests. Result: The loading efficacy was 46.66%. SFB-NK-Exos-treated spheroids showed higher cytotoxic effects (33%) and apoptotic population (44.9%). Despite the reduction of SFB concentration in the SFB-NK-Exos formulation, similar cytotoxic effects to those of free SFB were observed. Increased intracellular trafficking, sustained release of the drug and selective inhibitory effects demonstrated efficient navigation. Conclusion: This is the first report for SFB loading into NK-Exos, which led to significant cytotoxic intensification against cancer cells.

Publisher

Future Medicine Ltd

Subject

Development,General Materials Science,Biomedical Engineering,Medicine (miscellaneous),Bioengineering

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