Dioxepine-derived surface-capping gold nanoparticles (Dd-AuNPs) induces ROS-mediated apoptosis and cell cycle arrest in A549 human lung cancer cell line

Abstract

The current study exemplifies the synthesis of novel gold nanoformulations loaded with dioxepine derivative a secondary metabolite from lichen Parmotrema reticulatum utilizing a green approach proving an insight into the impregnation method. The characteristic features of synthesized dioxepine-derived gold NPs (Dd-AuNPs) were analyzed using FT-IR (Fourier Transform Infrared Spectroscopy); it elaborates on the presence of diverse groups with broadband at 3461 cm⁻¹ indicating the presence of the –OH group and the small dip at 2928 cm⁻¹ corresponds to the stretching vibrations of –CH of carbohydrates. The crystallinity of synthesized Dd-AuNPs displayed three distinctive peaks in the 2θ range based on the XRD (X-ray diffraction) pattern. The surface zeta potential of Dd-AuNPs was + 58 mV, which shows the prepared nanoparticle surface has high positive charges and also showed an average hydrodynamic diameter of 661 nm with a peak intensity of 88% using the dynamic light scattering technique. The study elaborates its characterization with SEM (scanning electron microscope) analysis which indicates that AuNPs were dispersed in the solution; as supplementary, the results of HRTEM (high-resolution transmission electron microscopy) were shown at different magnifications along with selected area electron diffraction (SAED) pattern with several morphologies such as spherical, triangular, and hexagonal which particle size ranges from 20 to 30 nm. The synthesized Dd-AuNPs effectively scavenged free radicals in a dose-dependent manner with 21–45% and 12–71% of DPPH (2,2-diphenyl-1-picrylhydrazyl) and FRAP (ferric ion reducing antioxidant power) assay respectively. In addition, in vitro studies exhibited high cytotoxic activity against the human lung cancer cell line (A549) with IC₅₀ value of 12 μg/mL using MTT (3-(4,5-dimethylthiozol-2-yl)-3,5- diphenyl tetrazolium bromide) assay and accompanied by AO/EtBr (acridine orange (AO) and ethidium bromide (EtBr)) and DAPI (4′,6-diamidino-2-phenylindole) staining methods to confirm the apoptosis, nuclear condensation, and fragmentation. Similarly, flow cytometry analysis results provide greater shreds of evidence demonstrating that apoptosis occurred during the S phase, which was further confirmed using caspase assay proving the occurrence of apoptosis. These results highlight the intriguing potential of synthesized Dd-AuNPs as an effective source of bioactive compounds with antioxidant and anticancer abilities, necessitating additional research into their potential therapeutic potential in lung cancer cell lines.

Graphical Abstract