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

• Main Authors: Naime Majidi Zolbanin (Author), Reza Jafari (Author), Jafar Majidi (Author), Fatemeh Atyabi (Author), Mehdi Yousefi (Author), Farhad Jadidi-Niaragh (Author), Leili Aghebati-Maleki (Author), Dariush Shanehbandi (Author), Mohammad-Sadegh Soltani Zangbar (Author), Alireza Mohajjel Nayebi (Author)
• Format: Book
• Published: Tabriz University of Medical Sciences, 2018-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2228-5881; 2251-7308; 10.15171/apb.2018.045
• Keywords: Aptamer; Chitosan; cMET siRNA; Docetaxel; Metastatic breast cancer; Therapeutics. Pharmacology; RM1-950
• Source: Advanced Pharmaceutical Bulletin, Vol 8, Iss 3, Pp 383-393 (2018)

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.