Peptide-derived gold nanoparticles as a promising delivery system for Src targeting siRNA in breast cancer cells†

Abstract

Src, a non-receptor tyrosine kinase, is involved in various cellular processes including cell division, motility, adhesion, angiogenesis, and survival. RNAi therapy, particularly siRNA, aims to silence genes essential for tumor growth, metastasis, and therapy resistance. In this study, previously developed linear peptides containing tryptophan and histidine/arginine were screened for synthesizing gold nanoparticles. The efficiency of the derived nanoparticles was investigated for nucleic acid delivery. The synthesized AuNPs were characterized using UV-visible spectroscopy, TEM, and DLS. Gel retardation assays demonstrated strong siRNA binding (90%) by gold nanoparticles compared to peptides alone (40%), specifically for peptide W4R4. FACS results revealed a 10-fold enhancement in the cellular uptake of fluorescence-tagged siRNA when delivered via nanoparticles compared to that of naked siRNA. Confocal microscopy confirmed siRNA localization primarily in the cytosol and partially in the nucleus. Western blot analysis indicated 78% downregulation of the Src protein in MCF-7 cells using AuNP/siRNA complexes. These results collectively indicate that the synthesized AuNPs are promising delivery systems for siRNA and might be a potential candidate for RNAi therapeutics.