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ABSTRACT
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.
Author contributions
Designed and performed the experiments, analyzed the data and wrote the paper: Dr. Gozde UNSOY. Contributed reagents, materials and analysis tools: Prof. Dr. Ufuk GUNDUZ.
Conflict of interest
The authors of this study declare that they have no conflict of interest.
Declaration of interests
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.