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Therapeutic potential of inhibiting ABCE1 and eRF3 genes via siRNA strategy using chitosan nanoparticles in breast cancer cells

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Abstract

In recent years, targeted cancer therapy strategies have begun to take the place of the conventional treatments. Inhibition of the specific genes, involved in cancer progress, via small interfering RNA (siRNA) has become one of the promising therapeutic approaches for cancer therapy. However, due to rapid nuclease degradation and poor cellular uptake of siRNA, a suitable carrier for siRNA penetration inside the cells is required. We used chitosan nanoparticles (CS-NPs) to efficiently deliver ATP-binding casette E1 (ABCE1) and eukaryotic release factor 3 (eRF3)-targeting siRNAs, individually and together, to reduce the proliferation and induce the apoptosis of breast cancer cells. The CS-NPs were generated by ionic gelation method using tripolyphosphate (TPP) as a crosslinker. Nanoparticles (NPs) were obtained with diameters ranging between 110 and 230 nm and the zeta potential of approximately 27 mV optimizing the solution pH to 4.5 and CS/TPP mass ratio to 3:1. Loading efficiencies of 98.69 % ± 0.051 and 98.83 % ± 0.047 were achieved when ABCE1 siRNA and eRF3 siRNA were entrapped into the NPs, respectively. Cell proliferation assay demonstrated that siRNA-loaded CS-NPs were more effective on cancer cells when compared to siRNAs without CS-NPs. Parallel results were also obtained by apoptosis/necrosis, double-staining analysis. Within our study, the potency of ABCE1 and eRF3 siRNAs were shown for the first time with this kind of polymeric delivery system. The results also indicated that ABCE1 and eRF3, important molecules in protein synthesis, could serve as effective targets to inhibit the cancer cells.

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Acknowledgments

Our study was financially supported by Hacettepe University, Scientific Research Projects Coordination Unit (Grant number 011A601003).

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Authors and Affiliations

  1. Nanotechnology and Nanomedicine Division, Hacettepe University, Beytepe, 06800, Ankara, Turkey

    Bagdat Burcu Cengiz & Mehmet Dogan Asik

  2. Biochemistry Division, Chemistry Department, Hacettepe University, Beytepe, 06800, Ankara, Turkey

    Goknur Kara & Emir Baki Denkbas

  3. Bioengineering Department, Kirikkale University, Yahsihan, 71451, Kirikkale, Turkey

    Mustafa Turk

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  1. Bagdat Burcu Cengiz
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  2. Mehmet Dogan Asik
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  3. Goknur Kara
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  4. Mustafa Turk
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  5. Emir Baki Denkbas
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Correspondence to Emir Baki Denkbas.

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Cengiz, B.B., Asik, M.D., Kara, G. et al. Therapeutic potential of inhibiting ABCE1 and eRF3 genes via siRNA strategy using chitosan nanoparticles in breast cancer cells. J Nanopart Res 17, 168 (2015). https://doi.org/10.1007/s11051-015-2980-y

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  • DOI: https://doi.org/10.1007/s11051-015-2980-y

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