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Therapeutic Potential of DNAzyme Loaded on Chitosan/Cyclodextrin Nanoparticle to Recovery of Chemosensitivity in the MCF-7 Cell Line

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Abstract

Commonly, acquired resistances to anticancer drug are mediated by overexpression of a membrane-associated protein that encode via multi-drug resistance gene-1 (MDR1). Herein, the mRNA-cleaving DNAzyme that targets the mRNA of MDR1 gene in doxorubicin-resistant breast cancer cell line (MCF-7/DR) loaded on the chitosan β-cyclodextrin complexes was used as a tropical agent. Chitosan/β-cyclodextrin complexes were used to deliver DNAzymes into cancer cells. Determination of the physicochemical characteristics of the particles was done by photon correlation spectroscopy and scanning electron microscopy. The encapsulation efficiency of the complexes was tested by using gel retardation assay. Positively charged nanoparticles interacted with DNAzyme that could perform as an efficient DNAzyme transfection system. The rationale usage of this platform is to sensitize MCF-7/DR to doxorubicin by downregulating the drug-resistance gene MDR1. Results demonstrated a downregulation of MDR1 mRNAs in MCF-7/DR/DNZ by real-time PCR, compared to the MCF-7/DR as control. WST1 assay showed the 22-fold decrease in drug resistance on treated cells 24 h after transfection. Results showed the intracellular accumulation of Rh123 increased in the treated cells with DNAzyme. Results suggested a potential platform in association with chemotherapy drug for cancer therapy and indicated extremely efficient at delivery of DNAzyme in restoring chemosensitivity.

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Funding

This study received a financial support from the Research Council of the Shahid Bahonar University of Kerman (Iran).

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Authors and Affiliations

  1. Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran

    Elham Zokaei, Arastoo Badoei-dalfrad & Zahra Karami

  2. Pharmaceutics Research Centre, Faculty of Pharmacy, Kerman University of Medical Sciences, Haft-Bagh Boulevard, PO Box 76175-439, Kerman, 7616931555, Iran

    Mehdi Ansari

  3. Department of Anatomy, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Touba Eslaminejad

  4. Pharmaceutics Research Centre, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Seyed Noureddin Nematollahi-Mahani

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  1. Elham Zokaei
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  2. Arastoo Badoei-dalfrad
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  3. Mehdi Ansari
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  4. Zahra Karami
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  5. Touba Eslaminejad
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  6. Seyed Noureddin Nematollahi-Mahani
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Correspondence to Arastoo Badoei-dalfrad or Mehdi Ansari.

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Zokaei, E., Badoei-dalfrad, A., Ansari, M. et al. Therapeutic Potential of DNAzyme Loaded on Chitosan/Cyclodextrin Nanoparticle to Recovery of Chemosensitivity in the MCF-7 Cell Line. Appl Biochem Biotechnol 187, 708–723 (2019). https://doi.org/10.1007/s12010-018-2836-x

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