Investigation of the Exosome-Based Drug Delivery System Potential in theTreatment of Glioblastoma in vitro Experimental Models

Yıl 2021, Cilt: 4 Sayı: 3, 451 - 467, 15.12.2021

Sıdıka Genç , Zeynep Çakır , Ali Taghizadehghalehjoughi , Yeşim Yeni , Kiyumars Jalili , Ahmet Hacımüftüoğlu

https://doi.org/10.38001/ijlsb.990646

Cited By: 1

Öz

In our study, it was aimed to create a new drug delivery system by loading the chemotherapeutic drugs into exosome vesicles. This system act as a Trojan horse to targeting GBM cancer. Exosomes were isolated from the T-98G cell line and characterized. Exosomes were encapsulated with Temozolomide. Then, the effectiveness of this new delivery system was evaluated by using MTT, LDH, TAC, TOS, GR.
MTT results show a dose-dependent decrease in the TMZ and Exolimer+TMZ groups. But this rate decreased significantly in the Exolimer+TMZ groups. The lowest viability was observed at the Exolimer+TMZ 800 ng/ml concentration. Our results in LDH, GR, TAS and TOS analyzes shows correlation with MTT.
Based on this study, we think that targeting the exosome to cancer by combining with special molecules and nanotechnology will bring a new perspective to cancer treatment.

Anahtar Kelimeler

Exosome, Glioblastoma, TEM, Temozolomide

Proje Numarası

TDK-2020-8442.

Kaynakça

• Referans1. Thakkar, J.P., et al., Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev, 2014. 23(10): p. 1985-96.
• Referans2. Blissitt, P.A., Clinical practice guideline series update: care of the adult patient with a brain tumor. J Neurosci Nurs, 2014. 46(6): p. 367-8.
• Referans3. Raposo, G. and W. Stoorvogel, Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol, 2013. 200(4): p. 373-83.
• Referans4. Al-Nedawi, K., et al., Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol, 2008. 10(5): p. 619-24.
• Referans5. Chen, Y., et al., Protein content and functional characteristics of serum-purified exosomes from patients with colorectal cancer revealed by quantitative proteomics. Int J Cancer, 2017. 140(4): p. 900-913.
• Referans6. Balaj, L., et al., Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun, 2011. 2: p. 180.
• Referans7. Valadi, H., et al., Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol, 2007. 9(6): p. 654-9.
• Referans8. Sato-Kuwabara, Y., et al., The fusion of two worlds: non-coding RNAs and extracellular vesicles--diagnostic and therapeutic implications (Review). Int J Oncol, 2015. 46(1): p. 17-27.
• Referans9. Taylor, D.D. and C. Gercel-Taylor, MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol, 2008. 110(1): p. 13-21.
• Referans10. Sousa, D., R.T. Lima, and M.H. Vasconcelos, Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles. Trends Mol Med, 2015. 21(10): p. 595-608.
• Referans11. Liu, D., et al., The Smart Drug Delivery System and Its Clinical Potential. Theranostics, 2016. 6(9): p. 1306-23.
• Referans12. Haque, S., et al., Disposition and safety of inhaled biodegradable nanomedicines: Opportunities and challenges. Nanomedicine, 2016. 12(6): p. 1703-24.
• Referans13. Luan, X., et al., Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin, 2017. 38(6): p. 754-763.
• Referans14. Taghizadehghalehjoughi, A., et al., Vincristine combination with Ca(+2) channel blocker increase antitumor effects. Mol Biol Rep, 2019. 46(2): p. 2523-2528.
• Referans15. Taghizadehghalehjoughi, A., et al., Combination of Pycnogenol and Melatonin Reduce PC-3 and HT29 Cell Migration: Comparison to the Actions of Cisplatin. Acta Scientific Pharmaceutical Sciences, 2020. 4(12): p. 176-188.
• Referans16. Taghizadehghalehjoughi, A., et al., Melatonin receptors increase Momordica’s anticancer effects against PC-3 and HT-29. J Contemp Med, 2021. 11(2): p. 166-173.
• Referans17. Huang, J., et al., Cancer cell-derived exosomes promote cell proliferation and inhibit cell apoptosis of both normal lung fibroblasts and non-small cell lung cancer cell through delivering alpha-smooth muscle actin. American Journal of Translational Research, 2019. 11(3): p. 1711.
• Referans18. Saadatpour, L., et al., Glioblastoma: exosome and microRNA as novel diagnosis biomarkers. Cancer Gene Ther, 2016. 23(12): p. 415-418.
• Referans19. Kalluri, R. and V.S. LeBleu, The biology, function, and biomedical applications of exosomes. Science, 2020. 367(6478).
• Referans20. Chevillet, J.R., et al., Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci U S A, 2014. 111(41): p. 14888-93.
• Referans21. Yin, J., et al., Exosomal transfer of miR-1238 contributes to temozolomide-resistance in glioblastoma. EBioMedicine, 2019. 42: p. 238-251.
• Referans22. Munoz, J.L., et al., Temozolomide resistance in glioblastoma cells occurs partly through epidermal growth factor receptor-mediated induction of connexin 43. Cell Death Dis, 2014. 5: p. e1145.
• Referans23. Emsen, B., A. Kaya, and A. Aslan, Cytotoxic, Genotoxic and Oxidative Effects of Cladonia furcata (Huds.) Schrad. on Human Peripheral Lymphocytes. Cumhuriyet Science Journal, 2018. 39(1): p. 169-180.
• Referans24. Tuzgen, S., et al., Relationship between DNA damage and total antioxidant capacity in patients with glioblastoma multiforme. Clin Oncol (R Coll Radiol), 2007. 19(3): p. 177-81.