Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model

  • Vahid Shafiei-Irannejad
  • Mahdi Rahimi
  • Mojtaba Zarei
  • Roshan Dinparast-isaleh
  • Saman Bahrambeigi
  • Alireza Alihemmati
  • Salman Shojaei
  • Zarrin Ghasemi
  • Bahman YousefiEmail author
Research Paper



Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems.


A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues.


The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization.


Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.


enhanced drug delivery doxorubicin toxicity MCF7 breast cancer cells polyelectrolyte carboxymethyl cellulose 



Alanine aminotransferase


Aspartate aminotransferase


Creatine kinase


Carboxymethyl cellulose






Drug delivery systems


Drug encapsulation efficiency


Drug loading efficiency


Dynamic light scattering




Differential scanning calorimetry


Ethylenediaminetetraacetic acid


Energy-dispersive X-ray spectroscopy


Enhanced permeability and retention


Fetal bovine serum


Fourier transform infrared PLGA


Lactate dehydrogenase


Multidrug resistance


Mean fluorescent intensity


Magnetic nanoparticles


3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphe-nyltetrazolium bromide




Roswell Park Memorial Institute 1640 growth medium


Scanning electron microscopy


Transmission Electron Microscopy


Vibrating-sample magnetometer




X-ray diffraction


Acknowledgments and Disclosures

We thank the Drug Applied Research Centre (DARC), Aging Research Institute, Physical Medicine and Rehabilitation Research Centre, Clinical Research Development Unit, Shohada Hospital, Tabriz University of Medical Sciences, Tabriz, Iran and Cellular and Molecular Research Centre, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran. The authors report no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Vahid Shafiei-Irannejad
    • 1
    • 2
  • Mahdi Rahimi
    • 3
    • 4
    • 5
  • Mojtaba Zarei
    • 6
  • Roshan Dinparast-isaleh
    • 1
  • Saman Bahrambeigi
    • 1
  • Alireza Alihemmati
    • 3
  • Salman Shojaei
    • 5
  • Zarrin Ghasemi
    • 5
  • Bahman Yousefi
    • 6
    Email author
  1. 1.Cellular and Molecular Research Center, Cellular and Molecular Medicine InstituteUrmia University of Medical SciencesUrmiaIran
  2. 2.Solid Tumor Research Center, Cellular and Molecular Medicine InstituteUrmia University of Medical SciencesUrmiaIran
  3. 3.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran
  4. 4.Aging Research Institute, Physical Medicine and Rehabilitation Research CentreTabriz University of Medical SciencesTabrizIran
  5. 5.Department of Organic and Biochemistry, Faculty of ChemistryUniversity of TabrizTabrizIran
  6. 6.Immunology Research CenterTabriz University of Medical SciencesTabrizIran

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