Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 8 3 2018 08 29 Targeted Co-Delivery of Docetaxel and cMET siRNA for Treatment of Mucin1 Overexpressing Breast Cancer Cells 383 393 10.15171/apb.2018.045 EN Naime Majidi Zolbanin https://orcid.org/0000-0001-7286-5319 Reza Jafari https://orcid.org/0000-0003-2036-9043 Jafar Majidi https://orcid.org/0000-0002-7343-7989 Fatemeh Atyabi https://orcid.org/0000-0002-9421-8750 Mehdi Yousefi https://orcid.org/0000-0003-0099-6728 Farhad Jadidi-Niaragh https://orcid.org/0000-0002-4641-882X Leili Aghebati-Maleki https://orcid.org/0000-0002-0044-5961 Dariush Shanehbandi https://orcid.org/0000-0002-9449-0607 Mohammad-Sadegh Soltani Zangbar Alireza Mohajjel Nayebi https://orcid.org/0000-0003-2911-7280 Journal Article 10.15171/apb.2018.045 2018 04 07 2018 06 20 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.