Adv Pharm Bull. 2018;8(3):383-393.
doi: 10.15171/apb.2018.045
  Abstract View: 122
  PDF Download: 181

Research Article

Targeted Co-Delivery of Docetaxel and cMET siRNA for Treatment of Mucin1 Overexpressing Breast Cancer Cells

Naime Majidi Zolbanin 1,2 ORCiD, Reza Jafari 3,4 ORCiD, Jafar Majidi 5,6 ORCiD, Fatemeh Atyabi 7,8 ORCiD, Mehdi Yousefi 5,6 ORCiD, Farhad Jadidi-Niaragh 5,6 ORCiD, Leili Aghebati-Maleki 5 ORCiD, Dariush Shanehbandi 5 ORCiD, Mohammad-Sadegh Soltani Zangbar 6, Alireza Mohajjel Nayebi 1,2 ORCiD

1 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Pharmacology and Toxicology Department, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
4 Immunology Research Center, Inflammation and Inflammatory Diseases Division, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
5 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
6 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
7 Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
8 Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

Purpose: Targeted treatment of breast cancer through combination of chemotherapeutic agents and siRNA had been drawing much attention in recent researches. This study was carried out to evaluate mucin1 aptamer-conjugated chitosan nanoparticles containing docetaxel and cMET siRNA on SKBR3 cells. Methods: Nano-drugs were characterized by transmission electron microscope, Zetasizer and loading efficiency calculation. siRNA entrapment onto nanoparticles, stability of siRNA-loaded nanoparticles and conjugation of mucin1 aptamer to nanoparticles were evaluated via separate electrophoresis. Cellular uptake of the targeted nanoparticles was evaluated through GFP-plasmid expression in mucin1+ SKBR3 vs. mucin1- CHO cells. Protein expression, cell viability and gene expression were assessed by Western Blotting, MTT assay, and Quantitative Real Time-PCR, respectively. Results: Characterization of nano-drugs represented the ideal size (110.5± 3.9 nm), zeta potential (11.6± 0.8 mV), and loading efficiency of 90.7% and 88.3% for siRNA and docetaxel, respectively. Different gel electrophoresis affirmed the conjugation of aptamers to nanoparticles and entrapment of siRNA onto nanoparticles. Increased cellular uptake of aptamer-conjugated nanoparticles was confirmed by GFP expression. cMET gene silencing was confirmed by Western Blotting. The significant (p ≤0.0001) impact of combination targeted therapy vs. control on cell viability was shown. Results of Quantitative Real Time-PCR represented a remarkably decreased (p ≤0.0001) expression of the studied genes involving in tumorigenicity, metastasis, invasion, and angiogenesis (STAT3, IL8, MMP2, MMP9, and VEGF) by targeted combination treatment vs. control. Conclusion: The mucin1 aptamer-conjugated chitosan nanoparticles, containing docetaxel and cMET siRNA, is suggested for treatment of mucin1+ metastatic breast cancer cells. However, further studies should be conducted on animal models.
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Submitted: 07 Apr 2018
Revised: 14 Jun 2018
Accepted: 20 Jun 2018
First published online: 29 Aug 2018
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