Bioinspired RGD-Functionalized Gold Nanoparticles for Integrin-Driven Interaction with Melanoma Cells

In this study, we investigated the physicochemical properties, biofunctionalization and internalization mechanisms of peptide-functionalized gold nanoparticles (GNPs), with a particular focus on a cyclic a_vβ₃ integrin-targeting ligand (cRGD), embedded in a scaffold comprising a gold-binding glycine-cysteine tetrapeptide (GCt) and a fluorescein isothiocyanate (FITC) dye.

The characterisation of the GNPs and their biofunctionalised counterparts (b-GNPs) was carried out by a series of techniques including dynamic light scattering (DLS), zeta potential (ζ) measurements, UV-visible (UV-vis) spectroscopy, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and theoretical modelling. Cellular uptake experiments were performed in human adenocarcinoma (HeLa, a_vβ₃ non-expressing cells, negative control) and metastatic melanoma (WM266, a_vβ₃-overexpressing cells, positive control) cells to assess receptor-mediated internalization.

The physicochemical characterisation confirmed the successful functionalisation of GNPs with the bioinspired multifunctional cRGD-GCt-FITC moiety. Detailed analysis of the nano-bio interface revealed distinct chemical states and evidence of charge transfer effects between the GNPs surface and the RGD-containing peptide. Cellular studies demonstrated selective uptake and preferential accumulation of b-GNPs in a_vβ₃-overexpressing cells, with RGD-functionalised GNPs inducing notable pro-apoptotic effects.

This work provides new understanding of biomimetic gold nanoparticles and highlights their potential in tumour selective strategies, particularly for integring-targeted theranostics, while addressing toxicity and targeting limitations of current RGD- and gold nanoparticle-based nanomedicine.