Stem cells derived exosomes as biological nano carriers for VCR sulfate for treating breast cancer stem cells.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
14 05 2024
14 05 2024
Historique:
received:
01
09
2023
accepted:
15
04
2024
medline:
15
5
2024
pubmed:
15
5
2024
entrez:
14
5
2024
Statut:
epublish
Résumé
Due to vincristine sulfate's (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24-) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo's in vivo effectiveness and safety and improve the loading and delivery strategies.
Identifiants
pubmed: 38744871
doi: 10.1038/s41598-024-59736-7
pii: 10.1038/s41598-024-59736-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
10964Informations de copyright
© 2024. The Author(s).
Références
Ferlay, J. et al. Cancer statistics for the year 2020: An overview. Int. J. Cancer 149, 778–789 (2021).
doi: 10.1002/ijc.33588
Moharil, R. B., Dive, A., Khandekar, S. & Bodhade, A. Cancer stem cells: An insight Rohit. J. oral Maxillofac. Pathol. 21, 244–251 (2017).
doi: 10.4103/jomfp.JOMFP_132_16
Phi, L. T. H. et al. Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int. https://doi.org/10.1155/2018/5416923 (2018).
doi: 10.1155/2018/5416923
pubmed: 29681949
pmcid: 5850899
Hassouna, Y., El-Bedwehi, A., Mohamed, A., Mostafa, W. & Omar, M. Stem cells in orthodontics : A review. Al-Azhar J. Dent. Sci. 21, 433–441 (2018).
doi: 10.21608/ajdsm.2018.71682
Abdallah, A. N., Shamaa, A. A. & El-Tookhy, O. S. Evaluation of treatment of experimentally induced canine model of multiple sclerosis using laser activated non-expanded adipose derived stem cells. Res. Vet. Sci. 125, 71–81 (2019).
doi: 10.1016/j.rvsc.2019.05.016
pubmed: 31152923
Shen, Z. et al. Effects of mesenchymal stem cell-derived exosomes on autoimmune diseases. Front. Immunol. https://doi.org/10.3389/fimmu.2021.749192 (2021).
doi: 10.3389/fimmu.2021.749192
pubmed: 35126345
pmcid: 8733928
Shan, X. Q. et al. Immunomodulation: The next target of mesenchymal stem cellderived exosomes in the context of ischemic stroke. World J. Stem Cells 15, 52–70 (2023).
doi: 10.4252/wjsc.v15.i3.52
pubmed: 37007453
pmcid: 10052343
He, J. et al. Exosomal targeting and its potential clinical application. Drug Deliv. Transl. Res. 12, 2385–2402 (2022).
doi: 10.1007/s13346-021-01087-1
pubmed: 34973131
pmcid: 9458566
Liang, Y., Duan, L., Lu, J. & Xia, J. Engineering exosomes for targeted drug delivery. Theranostics 11, 3183–3195 (2021).
doi: 10.7150/thno.52570
pubmed: 33537081
pmcid: 7847680
Yuan, Y. G. et al. Biogenesis, composition and potential therapeutic applications of mesenchymal stem cells derived exosomes in various diseases. Int. J. Nanomed. 18, 3177–3210 (2023).
doi: 10.2147/IJN.S407029
Selawry, O. S. & Hananian, J. Vincristine treatment of cancer in children. JAMA J. Am. Med. Assoc. 183, 741–746 (1963).
doi: 10.1001/jama.1963.03700090061010
Triarico, S. et al. Vincristine-induced peripheral neuropathy (Vipn) in pediatric tumors: Mechanisms, risk factors, strategies of prevention and treatment. Int. J. Mol. Sci. 22, 4112 (2021).
doi: 10.3390/ijms22084112
pubmed: 33923421
pmcid: 8073828
Škubník, J., Pavlíčková, V. S., Ruml, T. & Rimpelová, S. Vincristine in combination therapy of cancer: Emerging trends in clinics. Biology. 10, 849 (2021).
doi: 10.3390/biology10090849
pubmed: 34571726
pmcid: 8468923
Nunes, T. et al. Targeting cancer stem cells to overcome chemoresistance. Int. J. Mol. Sci. 19, 1–24 (2018).
doi: 10.3390/ijms19124036
Arnold, M. et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast 66, 15–23 (2022).
doi: 10.1016/j.breast.2022.08.010
pubmed: 36084384
pmcid: 9465273
Yalaza, M., İnan, A. & Bozer, M. Male breast cancer. J. breast Heal. 12, 1–8 (2016).
doi: 10.5152/tjbh.2015.2711
Liu, Y. & Feng, N. Nanocarriers for the delivery of active ingredients and fractions extracted from natural products used in traditional Chinese medicine (TCM). Adv. Colloid Interface Sci. 221, 60–76 (2015).
doi: 10.1016/j.cis.2015.04.006
pubmed: 25999266
Liu, X. & Quan, N. Immune cell isolation from mouse femur bone marrow. Bio-Protocol https://doi.org/10.21769/BioProtoc.1631 (2015).
doi: 10.21769/BioProtoc.1631
pubmed: 27441207
Soleimani, M. & Nadri, S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat. Protoc. 4, 102–106 (2009).
doi: 10.1038/nprot.2008.221
pubmed: 19131962
Kadekar, D., Kale, V. & Limaye, L. Differential ability of MSCs isolated from placenta and cord as feeders for supporting ex vivo expansion of umbilical cord blood derived CD34+ cells. Stem Cell Res. Ther. https://doi.org/10.1186/s13287-015-0194-y (2015).
doi: 10.1186/s13287-015-0194-y
pubmed: 26481144
pmcid: 4617445
Ramos, T. L. et al. MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry. Cell Commun. Signal. 14, 1–14 (2016).
doi: 10.1186/s12964-015-0124-8
Haney, M. J. et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. Control Release 207, 18–30 (2015).
doi: 10.1016/j.jconrel.2015.03.033
Skehan, P. et al. New colorimetric cytotoxicity assay for anticancer-drug screening. JNCI J. Natl. Cancer Inst. 82(13), 1107–1112. https://doi.org/10.1093/jnci/82.13.1107 (1990).
doi: 10.1093/jnci/82.13.1107
pubmed: 2359136
Allam, R. M. et al. SC. Toxicol. Lett. https://doi.org/10.1016/j.toxlet.2018.04.008 (2018).
doi: 10.1016/j.toxlet.2018.04.008
pubmed: 29654831
Tiwari, G. et al. Drug delivery systems: An updated review. Int. J. Pharm. Investig. 2, 2 (2012).
doi: 10.4103/2230-973X.96920
pubmed: 23071954
pmcid: 3465154
Patra, J. K. et al. Nano based drug delivery systems: Recent developments and future prospects. J. Nanobiotechnol. 16, 1–33 (2018).
doi: 10.1186/s12951-018-0392-8
Edgar, J. R. Q & A: What are exosomes, exactly?. BMC Biol. 14, 1–7 (2016).
doi: 10.1186/s12915-016-0268-z
Gebeyehu, A., Kommineni, N., Meckes, D. G. & Sachdeva, M. S. Role of exosomes for delivery of chemotherapeutic drugs. Crit. Rev. Ther. Drug Carrier Syst. 38, 53–97 (2021).
doi: 10.1615/CritRevTherDrugCarrierSyst.2021036301
pubmed: 34375513
pmcid: 8691065
Kibria, G. et al. HHS Public Access. 15, 3625–3633 (2019).
Vikram, R., Chou, W., Hung, S. & Shen, C. Tumorigenic and metastatic role of CD44 − /. Cancers 12, 1–23 (2020).
doi: 10.3390/cancers12051239
Venugopal, C. et al. Dosage and passage dependent neuroprotective effects of exosomes derived from rat bone marrow mesenchymal stem cells: An in vitro analysis. Curr. Gene Ther. https://doi.org/10.2174/1566523218666180125091952 (2018).
doi: 10.2174/1566523218666180125091952
pubmed: 30209999
Chekhun, S., Bezdenezhnykh, N., Shvets, J. & Lukianova, N. Expression of biomarkers related to cell adhesion, metastasis and invasion of breast cancer cell lines of different molecular subtype. Exp. Oncol. 35, 174–179 (2013).
pubmed: 24084454
Ali, N. M. et al. Adipose mscs suppress mcf7 and mda-mb-231 breast cancer metastasis and emt pathways leading to dormancy via exosomal-mirnas following co-culture interaction. Pharmaceuticals 14, 1–29 (2021).
Zhou, J. et al. Mesenchymal stem cell derived exosomes in cancer progression, metastasis and drug delivery: A comprehensive review. J. Cancer 9, 3129–3137 (2018).
doi: 10.7150/jca.25376
pubmed: 30210636
pmcid: 6134817
Liu, Y. et al. Exosomes and their role in cancer progression. Front. Oncol. 11, 1–9 (2021).
Gutierrez-Millan, C., Calvo Díaz, C., Lanao, J. M. & Colino, C. I. Advances in exosomes-based drug delivery systems. Macromol. Biosci. 21, 1–19 (2021).
doi: 10.1002/mabi.202000269
Kim, H. et al. Recent advances in exosome-based drug delivery for cancer therapy. Cancers 13, 1–23 (2021).