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Effect of platelet exosomes loaded with doxorubicin as a targeted therapy on triple-negative breast cancer cells

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Abstract

Exosomes have come to the fore in drug delivery systems due to their biological-based and immune-suppressing properties. In this study, we investigated the effect of doxorubicin loading of exosomes isolated from human platelets on breast cancer.

Exosomes released from ADP (1 µM)-activated platelets were isolated by the ultracentrifugation method, and their size and charge were measured with a TEM and zeta sizer. Then doxorubicin (Dox) loading into exosomes (PLT-Exo-Dox) was done by electroporation and incubated with MDA-MB-231 cells. In exosome characterization, CD62 positivity was higher in platelet pellets, while CD9 positivity was higher in released exosomes. The size of PLT-Exo and PLT-Exo-Dox was 82.02 ± 5.21 nm and 116 ± 3.73 nm, with a polydispersity index of 0.26 ± 0.04 and 0.39 ± 0.06, and the Zeta potential was − 16.45 mV and 24.07 mV, respectively. The encapsulation efficiency of the preparation was 86.02 ± 6.16%, with a drug loading capacity of 4.75 ± 0.16 µg/µg of the exosome. In MDA-MB-231 cells, PLT-Exo increased cell viability, while PLT-Exo-Dox decreased in 24 h. The Annexin-V binding level and Bax gene expression were increased in PLT-Exo-Dox and Bcl-2 gene expression was decreased. This study will shed light on the development of release systems that can be effective with chemotherapeutic agents by using exosomes released by cells in the development of personalized treatments.

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Data Availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by Aydin Adnan Menderes University Research Grant (ADU-TPF-20042).

Funding

This work was supported by Aydin Adnan Menderes University Research Grant (ADU-TPF-20042).

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Authors and Affiliations

  1. Department of Molecular Biotechnology, Graduate School of Health Sciences, Aydin Adnan Menderes University, Aydin, Turkey

    Dilara Uslu

  2. Department of Medicinal Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, Turkey

    Burcin Irem Abas & Ozge Cevik

  3. Department of Pharmaceutical Technology, Faculty of Pharmacy, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey

    Gulen Melike Demirbolat

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by DU, BIA, GMD. The first draft of the manuscript was written by OC and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ozge Cevik.

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Ethical approval

This study was approved from Adnan Menderes University Ethics Committee (53043469-050.04.04/12). All methods were performed in accordance with the relevant guidelines and regulations and were approved by our ethics committee.

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Uslu, D., Abas, B.I., Demirbolat, G.M. et al. Effect of platelet exosomes loaded with doxorubicin as a targeted therapy on triple-negative breast cancer cells. Mol Divers 28, 449–460 (2024). https://doi.org/10.1007/s11030-022-10591-6

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