Evaluation of anticancer effects of NL2-targeted polycationic nanoparticles containing decoy oligodeoxynucleotide against Nanog in breast cancer cell line (SKBR3)
Evaluation of anticancer effects of NL2-targeted polycationic nanoparticles containing decoy oligodeoxynucleotide against Nanog in breast cancer cell line (SKBR3)
Roghayeh Ghorbani,1Benyamin Keshavarz,2Zeinab Pourmansouri,3Hamid Madanchi,4Behrooz Johari,5,*
1. Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences 2. Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences 3. Department of Pharmacology, School of Medicine, Zanjan University of Medical Sciences 4. Department of Medical Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences 5. Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences
Introduction: Aberrant expression of NANOG in cancer stem cells (CSCs) has been linked to resistance against conventional therapeutic strategies in certain types of cancer. In the present study, we explored the anticancer effects of silica nanoparticles coated with poly(l-DOPA), labeled with NL-2 peptide, and containing NANOG decoy oligodeoxynucleotides on SKBR3 breast cancer cells.
Methods: NANOG decoy oligodeoxynucleotides, designed and synthesized based on the Sox2 gene promoter, were loaded on SiO2@PDOPA-NL2 nanocomposites. The physicochemical properties of these nanocomposites were investigated using FTIR, DLS, SEM, and release tests. The NL2 peptide was used to increase the selectivity of drug delivery to HER2-positive tumor cells. Subsequently, the cellular uptake of these nanocomposites was evaluated through an uptake test, and their anticancer properties were investigated using MTT, cell cycle, apoptosis, and scratch assays on the SKBR3 cell line.
Results: The tests related to the physicochemical properties of the nanocomposite showed nanometer size, spherical shape, and correct synthesis. The release of ODNs from the nanocomposites was time-dependent, with the peak release occurring at 24 hours. The NL2-targeted nanocomposites were efficiently taken up by SKBR3 cells, targeting the HER2 receptor. The effects of nanocomposite treatment showed significant cell growth inhibition, apoptosis induction, and cell cycle arrest.
Conclusion: The results suggested that SiO2@PDOPA-DEC-NL2 can potentially suppress the proliferation of SKBR3 cells. Therefore, the presented nanocomposite system can be a promising approach for targeted drug delivery in cancer treatment.
Keywords: decoy oligodeoxynucleotides, NANOG, NL-2 peptide, silica nanoparticle, breast cancer.