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Apoptotic Effects of Mucin1 Aptamer-Conjugated Nanoparticles Containing Docetaxel and C-Met Sirna on Skbr3 Human Metastatic Breast Cancer Cells Publisher



Zolbanin NM1, 2 ; Jafari R3, 4 ; Majidi J5 ; Atyabi F7, 8 ; Yousefi M5 ; Jadidiniaragh F5 ; Zangbar MSS6 ; Asadi M5 ; Nayebi AM2, 9
Authors
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Authors Affiliations
  1. 1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
  2. 2. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  3. 3. Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
  4. 4. Department of Immunology and Genetics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
  5. 5. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
  6. 6. Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  7. 7. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

Source: Jundishapur Journal of Natural Pharmaceutical Products Published:2019


Abstract

Background: Apoptosis is a crucial process in the failure of cancer progression. However, the occurrence of resistance to chemotherapy in cancer cells may prevent apoptosis via induction of the expression of the anti-apoptotic genes (Bcl-2) and/or reduction of the expression of the apoptotic caspases. Objectives: The current study aimed at investigating the apoptotic effects of targeted co-delivery of docetaxel and cMet siRNA (siMet) through mucin1 aptamer-conjugated chitosan nanoparticles on mucin1 + metastatic breast cancer cells (SKBR3). Methods: Characterization of nano-drugs, Western blotting assay, annexin V/ propidium iodide staining assay, and gene expression studies were evaluated based on metastatic breast cancer cells. Results: Characterization showed the appropriate size (110.5 ± 3.9 nm), zeta potential (11.6 ± 0.8 mV), and spherical shape of nanoparticles. Loading efficiency of 90.7% and 88.3% were gained for siRNA and docetaxel, respectively. The siRNA entrapment onto nanoparticles and conjugation of aptamers to nanoparticles were confirmed by gel electrophoresis. Gene knockdown assay represented the effectiveness of siMet on cMet gene silencing. According to the flow cytometry results, targeted co-delivery was successful in leading tumor cells to apoptosis (94.9%). Also, targeted co-delivery could reduce the expression of Bcl-2 gene (P < 0.0001) and increase the expression of caspase-8 and caspase-9 genes (P < 0.0001). Conclusions: Combination treatment of metastatic breast cancer cells with aptamer-conjugated nanoparticles containing docetaxel and cMet siRNA significantly increased apoptosis. © 2019 Genetics Society of America. All rights reserved.