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.