The effect of 5-fluorouracil loaded albumin magnetic nanoparticles on viability and cell cycle of human breast cancer MCF-7 cell line

Rajabi, Zahra; Bagheri, Fatemeh; Shojaosadati, Seyed Abbas

The effect of 5-fluorouracil loaded albumin magnetic nanoparticles on viability and cell cycle of human breast cancer MCF-7 cell line

Document Type : Original Research

Authors

Z. Rajabi ¹

F. Bagheri ²

S. A. Shojaosadati ²

¹ Department of Biomedical Engineering, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran

² Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran

Abstract

Abstract

Research Subject: Breast cancer is one of the most common cancer in the world with the highest mortality rate in women. Chemotherapy is the typical therapy for the cancer. However, it has side effects due to damage to healthy cells. Targeted drug delivery by nano carriers to the cancerous cells reduces the toxic side effects on normal cells. Serum albumin is a widely used drug carrier because of its availability, ease of preparation, and binding ability to various ligands. Attachment of iron oxide nanoparticles to albumin can control their distribution by applying an external magnetic field.

Research Approach: In this study, albumin nanoparticles attached to superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized and loaded with 5-Fluorouracil (5-FU) anticancer drug by using the desolvation technique. The produced nanoparticles were characterized in terms of size, surface charge, and drug entrapment, by dynamic light scattering (DLS) and UV-Vis spectrophotometry. The cytotoxic effects of 5FU-loaded magnetic albumin nanoparticles and free 5FU on MCF7 cells were evaluated with the MTT assay. The internalization of nanoparticles in MCF-7 cells was confirmed by Prussian blue staining. In the end, the effects of nanoparticles on cell cycle and apoptosis were evaluated by flow cytometry using propidium iodide.

Main Results: The mean particle size and zeta potential of 5FU loaded albumin nanoparticles and albumin magnetic nanoparticles were 220 nm, -25.8 mV, and 221 nm, -28 mV respectively. Drug entrapment efficiency and drug loading efficiency were also, 20%, 1%, and 15.8%, and 0.06% for albumin nanoparticles and magnetic albumin nanoparticles in turn. The drug-loaded magnetic albumin nanoparticles showed higher cytotoxicity than the free drug on MCF-7 cells. The flow cytometry cell cycle analysis showed more cytotoxicity of albumin nanoparticles in comparison with other groups. According to these results, it can be said that 5-FU loaded magnetic albumin nanoparticles were more effective and deserve further studies in the cancer treatment.

Keywords: Albumin magnetic nanoparticles, 5-fluorouracil, targeted drug delivery, MCF-7 cell line

Keywords

Albumin magnetic nanoparticles

5-flurouracil

MCF-7 cell line

targeted drug delivery

Subjects

Drug delivery

[1] Hossen S, Hossain MK, Basher M, Mia M, Rahman M, Uddin MJ. Smart nanocarrier-based drug delivery systems for cancer therapy and toxicity studies: A review. Journal of advanced research 15:1-18, 2019
[2] Ak G, Yɪlmaz H, Sanlɪer SH. Preparation of magnetically responsive albumin nanospheres and in vitro drug release studies. Artificial cells, nanomedicine, and biotechnology 42:18-26, 2014
[3] Armstrong K, Eisen A, Weber B. Assessing the risk of breast cancer. New England Journal of Medicine 342:564-71, 2000
[4] Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Advanced drug delivery reviews 55:329-47, 2003
[5] Singhvi G, Rapalli VK, Nagpal S, Dubey SK, Saha RN. Nanocarriers as potential targeted drug delivery for cancer therapy. In Nanoscience in Medicine Vol. 1:51-88: Springer. Number of 51-88 pp, 2020
[6] Lohcharoenkal W, Wang L, Chen YC, Rojanasakul Y. Protein nanoparticles as drug delivery carriers for cancer therapy. BioMed research international , 1-12, 2014
[7] Martínez-López AL, Pangua C, Reboredo C, Campión R, Morales-Gracia J, Irache JM. Protein-based nanoparticles for drug delivery purposes. International Journal of Pharmaceutics, 581, 119289, 2020
[8] Karami E, Behdani M, Kazemi-Lomedasht F. Albumin nanoparticles as nanocarriers for drug delivery: Focusing on antibody and nanobody delivery and albumin-based drugs. Journal of Drug Delivery Science and Technology 55:101471, 2020
[9] Ulbrich K, Michaelis M, Rothweiler F, Knobloch T, Sithisarn P. Interaction of folate-conjugated human serum albumin (HSA) nanoparticles with tumour cells. International journal of pharmaceutics 406:128-34, 2011
[10] Kouchakzadeh H, Hoseini MS, Shojaosadati S. Simultaneous loading of 5-florouracil and SPIONs in HSA nanoparticles: Optimization of preparation, characterization and in vitro drug release study. 35-42, 2016
[11] Andrade Â, Ferreira R, Fabris J, Domingues R. Coating nanomagnetic particles for biomedical applications. Biomedical Engineering—Frontiers and Challenges, 2011
[12] Estelrich J, Escribano E, Queralt J, Busquets MA. Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery. International journal of molecular sciences 16:8070-101, 2015
[13] Ito A, Shinkai M, Honda H, Kobayashi T.. Medical application of functionalized magnetic nanoparticles. Journal of bioscience and bioengineering 100:1-11, 2005
[14] Avval ZM, Malekpour L, Raeisi F, Babapoor A, Mousavi SM. Introduction of magnetic and supermagnetic nanoparticles in new approach of targeting drug delivery and cancer therapy application. Drug Metabolism Reviews 52:157-84, 2020
[15] Zeybek A, Şanlı‐Mohamed G, Ak G, Yılmaz H, Şanlıer ŞH. In vitro Evaluation of Doxorubicin‐Incorporated Magnetic Albumin Nanospheres. Chemical Biology & Drug Design 84:108-15, 2014
[16] Asara Y, Marchal JA, Carrasco E, Boulaiz H, Solinas G. Cadmium modifies the cell cycle and apoptotic profiles of human breast cancer cells treated with 5-fluorouracil. International journal of molecular sciences 14:16600-16, 2013
[17] Maghsoudi A, Shojaosadati SA, Farahani EV. 5-Fluorouracil-loaded BSA nanoparticles: formulation optimization and in vitro release study. Aaps Pharmscitech 9:1092-6, 2008
[18] Huang P, Li Z, Hu H, Cui D. Synthesis and characterization of bovine serum albumin-conjugated copper sulfide nanocomposites. Journal of Nanomaterials, 2010
[19] Bagheri F, Safarian S, Eslaminejad MB, Sheibani N. siRNA-mediated knock-down of DFF45 amplifies doxorubicin therapeutic effects in breast cancer cells. Cellular Oncology 36:515-26, 2013
[20] Zolnik BS, González-Fernández Á, Sadrieh N, Dobrovolskaia MA. Minireview: nanoparticles and the immune system. Endocrinology. 151(2):458-65, 2010
[21] Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari MR. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 10(2):57, 2018
[22] Frei E. Albumin binding ligands and albumin conjugate uptake by cancer cells. Diabetology & metabolic syndrome. 3(1):1-4, 2011
[23] Kratz F, Elsadek B. Clinical impact of serum proteins on drug delivery. Journal of Controlled Release, 161(2):429-45, 2012
[24] Setayesh A, Bagheri F, Boddohi S. Self-assembled formation of chondroitin sulfate-based micellar nanogel for curcumin delivery to breast cancer cells. International Journal of Biological Macromolecule , 161:771-778, 2020
[25] Saleh E, El-Awady R, Anis N. Predictive markers for the response to 5-fluorouracil therapy in cancer cells: Constant-field gel electrophoresis as a tool for prediction of response to 5-fluorouracil-based chemotherapy. Oncology letters 5:321-7, 2013