Peptide surface structure flexibility controls gold nanoparticle uptake in triple-negative breast cancer cells

Peptide-functionalized gold nanoparticles (AuNPs) provide a model for decoding how the surface-bound secondary structure regulates nano-bio interactions. AuNPs (30-40 nm) coated with small peptides, GSH, ECECG, GSSG and cyclic CEIEIEC exhibited a progressive increment in antiparallel β-sheet content (37-89%) upon surface binding with an increase in the number of amino acids. Cellular studies in MDA-MB-231 cells revealed efficient uptake for flexible, mixed-structure coronas (GSH, ECECG, GSSG), while the rigid, antiparallel β-sheet-dominant cyclic CEIEIEC corona suppressed internalization despite full cytocompatibility. These findings suggest that peptide conformational adaptability is associated with cellular entry, suggesting a clear structure-uptake relationship for the design of peptide-AuNP nanocarriers in aggressive breast cancer.