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

Area of Science:

• Nanomedicine
• Biomaterials Science
• Molecular Targeting

Background:

• Gold nanoparticles (GNPs) offer versatile platforms for biomedical applications.
• Targeted delivery systems are crucial for enhancing therapeutic efficacy and reducing side effects.
• Integrin receptors, such as αvβ3, are overexpressed in various cancers, making them attractive targets.

Purpose of the Study:

• To investigate the physicochemical properties, biofunctionalization, and cellular internalization mechanisms of peptide-functionalized gold nanoparticles (GNPs).
• To focus on a cyclic αvβ3 integrin-targeting ligand (cRGD) integrated with a gold-binding peptide (GCt) and a fluorescent dye (FITC).
• To evaluate the potential of these targeted GNPs for tumor-selective theranostics.

Main Methods:

• Characterization of GNPs and biofunctionalized GNPs (b-GNPs) using DLS, zeta potential, UV-vis spectroscopy, SEM, FTIR, and XPS.
• Theoretical modeling to understand nano-bio interface interactions.
• Cellular uptake studies in αvβ3-expressing (WM266 melanoma) and non-expressing (HeLa adenocarcinoma) cells to assess receptor-mediated internalization.

Main Results:

• Successful functionalization of GNPs with the cRGD-GCt-FITC moiety was confirmed.
• Analysis revealed distinct chemical states and charge transfer at the nano-bio interface.
• Selective uptake and accumulation of b-GNPs were observed in αvβ3-overexpressing cells, with RGD-functionalized GNPs inducing pro-apoptotic effects.

Conclusions:

• Biomimetic gold nanoparticles functionalized with cRGD show promise for tumor-selective targeting.
• This approach addresses limitations in current RGD- and gold nanoparticle-based nanomedicine regarding toxicity and targeting.
• The findings highlight potential for developing targeted theranostic strategies for cancer treatment.