Investigating the Antitumor Efficacy of NL2 Peptide‐Conjugated Silica Nanoparticles Loaded with NANOG Decoy Oligodeoxynucleotides for Targeted Delivery into Breast Cancer Cells

Abstract NANOG transcription factor, a molecule associated with cancer cell resistance, was targeted using decoy oligodeoxynucleotides (ODNs) loaded nanoparticles. We designed decoy ODN to mimic a human gene promoter, aiming to disrupt the function of NANOG. Silica (SiO 2 ) nanoparticles were coated with polydopamine (PDOPA) and loaded with decoy ODNs. These nanoparticles were then functionalized with a targeting agent, the NL2 peptide, to achieve specific binding to HER2‐positive cells. Following this, their physicochemical properties were characterized using Fourier‐transform infrared spectroscopy (FT‐IR), dynamic light scattering (DLS), scanning electron microscopy (SEM), UV–visible spectroscopy (UV–vis), and drug release assays. The effectiveness of these nanoparticles was then tested on SKBR3 (HER2 positive) and MDA‐MB‐468 (HER2 negative) breast cancer cells. The results were encouraging the nanocomposites were successfully absorbed by the cancer cells. SiO 2 @PDOPA/DEC‐NL2 significantly inhibits cell growth and increased cell death (apoptosis). These findings suggest that the synthesized nanosystem targeting the HER2 receptor can potentially suppress the cancerous properties of SKBR3 cells in comparison with MDA‐MB‐468 cells. In conclusion, this study presents a promising approach for targeted drug delivery in breast cancer treatment. The developed nanoparticles loaded with NANOG decoy ODNs effectively targeted HER2‐positive cancer cells and demonstrated significant anticancer properties.