Background: The aim of this study was to silence Survivin expression, related with drug-resistance, via siRNA-loaded CS-MNPs.
Methods and results: The highest siRNA-loading efficiency was achieved at siRNA:CS-MNP ratio of 1:2. Nanoparticles had spherical morphology and homogenous size distribution in TEM. After siRNA loading, core sizes (3-5 nm) of CS-MNPs didn't change significantly, however hydrodynamic diameters increased ~10 nm, indicating swelling of chitosan coat due to efficient siRNA loading. 73% of siRNA was pH-dependently released at 24hours, after 30% burst release at first 3.5hours. Stability was high enough to keep siRNAs in CS-MNPs at pH7.2. Cellular-internalization of Survivin-siRNA-CS-MNPs was high and localized in cytoplasm of cells.
Conclusion: Although, mock-siRNA loaded/unloaded CS-MNPs weren't cytotoxic, cell-death of breast cancer cells was significantly increased, after the treatment of Survivin-siRNA-loaded CS-MNPs. This reveals, successful loading of Survivin-siRNA on CS-MNPs and significant silencing of Survivin expression by triggering cell-death. Consequently, CS-MNPs are highly efficient delivery systems for intact siRNAs.
Keywords: Chitosan; doxorubicin resistant MCF-7 cells; magnetic nanoparticles; survivin siRNA; targeted drug delivery.