Synthesis of nanoliposomes containing green tea Catechin and doxorubicin to evaluate its toxicity on breast cancer cells

Document Type : Original Research

Authors

1 Biophysics Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran

2 Nanobiotechnology Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran

3 Biophysics-Nanobiotechnology Department, Biological Sciences Faculty, Tarbiat Modares University, Tehran, Iran

Abstract
Chemotherapy is one of the most effective and common treatments for cancer. Multi-drug resistance and drug side effects are one of the major obstacles to successful chemotherapy. To address these limitations and achieve better drug efficacy, nanosystem-based combination therapy offers a promising approach. This study aimed to synthesize, characterize, and investigate the synergistic effect of nanoliposomes loaded with doxorubicin and epigallocatechin-3-gallate (EGCG) on MCF-7 breast cancer cell lines. In the present study, nanoliposomes were prepared by passive loading and thin-film hydration. The characterization of nanoliposomes such as size distribution, zeta potential, the loading rate, drug release profile, and toxicity were measured. The mean diameter of nanoliposomes was 82.5 nm, their surface charge was -24.2 mV and drug loading was about 80%. The interaction of doxorubicin and EGCG with nanoliposomes was mediated by electrostatic and van der Waals bonds and EGCG has a deceasing effect on the doxorubicin release profile but the observed differences are not significant. The toxicity and viability data indicate that the simultaneous use of these two drugs increased the toxicity of the cells. Nanoliposomes containing doxorubicin were not able to reduce viability to below 50% in monotherapy with 5×10-3 μM. While, the amount of viability dramatically reduced to below 50%, in combination with EGCG, resulting as combination chemotherapy. Consequently, the concomitant administration of EGCG with doxorubicin may be a suitable candidate for chemotherapy.

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1. Tacar, O., P. Sriamornsak, and C.R. Dass, Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. Journal of pharmacy and pharmacology, 2013. 65(2): p. 157-170.
2. Cheng, T., et al., Green tea catechin-based complex micelles combined with doxorubicin to overcome cardiotoxicity and multidrug resistance. Theranostics, 2016. 6(9): p. 1277.
3. Hu, Y.-P., N. Henry-Toulme, and J. Robert, Failure of liposomal encapsulation of doxorubicin to circumvent multidrug resistance in an in vitro model of rat glioblastoma cells. European Journal of Cancer, 1995. 31(3): p. 389-394.
4. Yang, C.S., et al., Cancer prevention by tea: animal studies, molecular mechanisms and human relevance. Nature Reviews Cancer, 2009. 9(6): p. 429.
5. Li, W., et al., A major green tea component,(−)-epigallocatechin-3-gallate, ameliorates doxorubicin-mediated cardiotoxicity in cardiomyocytes of neonatal rats. Journal of agricultural and food chemistry, 2010. 58(16): p. 8977-8982.
6. Navarro, G., et al., P-glycoprotein silencing with siRNA delivered by DOPE-modified PEI overcomes doxorubicin resistance in breast cancer cells. Nanomedicine, 2012. 7(1): p. 65-78.
7. Jodoin, J., M. Demeule, and R. Béliveau, Inhibition of the multidrug resistance P-glycoprotein activity by green tea polyphenols. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2002. 1542(1-3): p. 149-159.
8. Sesarman, A., et al., Co-delivery of curcumin and doxorubicin in PEGylated liposomes favored the antineoplastic C26 murine colon carcinoma microenvironment. Drug delivery and translational research, 2019. 9(1): p. 260-272.
9. Chatterjee, K., et al., Doxorubicin cardiomyopathy. Cardiology, 2010. 115(2): p. 155-162.
10. Friedman, M., Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas. Molecular nutrition & food research, 2007. 51(1): p. 116-134.
11. Xiang, L.-P., et al., Suppressive effects of tea catechins on breast cancer. Nutrients, 2016. 8(8): p. 458.
12. Tsai, L.-C., et al., EGCG/gelatin-doxorubicin gold nanoparticles enhance therapeutic efficacy of doxorubicin for prostate cancer treatment. Nanomedicine, 2016. 11(1): p. 9-30.
13. Gu, J.-W., et al., EGCG, a major green tea catechin suppresses breast tumor angiogenesis and growth via inhibiting the activation of HIF-1α and NFκB, and VEGF expression. Vascular cell, 2013. 5(1): p. 9.
14. Stearns, M.E., et al., Combination therapy with epigallocatechin-3-gallate and doxorubicin in human prostate tumor modeling studies: inhibition of metastatic tumor growth in severe combined immunodeficiency mice. The American journal of pathology, 2010. 177(6): p. 3169-3179.
15. Ray, L., P. Kumar, and K.C. Gupta, The activity against Ehrlich's ascites tumors of doxorubicin contained in self assembled, cell receptor targeted nanoparticle with simultaneous oral delivery of the green tea polyphenol epigallocatechin-3-gallate. Biomaterials, 2013. 34(12): p. 3064-3076.