Cytotoxic Potential of Biogenic Gold Nanoparticles Functionalized With Brazilian Red Propolis in Prostate Cancer Cell Models

ABSTRACT Gold nanoparticles (GNPs) have been investigated for their potential application in medicine. GNPs can be synthesized by various methods, including green synthesis, a simple, low‐cost, and environment‐friendly methodology that provides an easy way to coat the nanoparticle's surface with natural molecules. Functionalization of the surface of GNPs with natural ligands that have pharmacological activities, such as Brazilian red propolis (BRP) extract, expands their biomedical applications, especially in cancer treatment. Therefore, the objective of this research was to investigate the cytotoxic activity of biogenic gold nanoparticles functionalized with BRP extract in vitro on prostate cancer (PCa) models. To achieve this, spherical GNPs were prepared by green synthesis using BRP extract (BRP‐GNPs) as a reducing and stabilizing agent. The formulation was characterized by dynamic light scattering (DLS), demonstrating a monomodal size distribution and negative zeta potential. X‐ray photoelectron spectroscopy (XPS) and small angle x‐ray scattering (SAXS) analyses indicated the existence of BRP organic compounds on the GNP's surface and the presence of aggregates. BRP‐GNPs showed cytotoxic activity against prostate cancer cells (PC3 and LNCaP), exhibiting IC 50 values of 45.09 and 95.15 μg/mL, respectively. The nanoparticles were able to inhibit cell proliferation, arrest the cell cycle, and trigger cell death through apoptosis and necrosis mechanisms. Compared with the 2D (monolayer) culture model, BRP‐GNPs exhibited a greater cytotoxic effect and cellular internalization in 3D (spheroid) culture models of PCa. Our study has demonstrated that the combination of BRP and GNPs is a promising candidate for antitumor and preventive applications against PCa.