Myco-nanotechnological approach to synthesize gold nanoparticles using a fungal endophyte, Penicillium oxalicum, and unravelling its antibacterial activity and anti-breast cancer role via metabolic reprogramming

The present study has been designed to fabricate fungal endophyte-assisted gold nanoparticles (AuNPs) and elucidate their anti-breast cancer potential. The aqueous extract of fungal endophyte<i>Penicillium oxalicum</i>(PO), associated with the medicinal plant<i>Amoora rohituka</i>, was used for the fabrication of AuNPs (POAuNPs). Physico-chemical characterization using Ultraviolet-visible spectroscopy, Fourier transform infrared, X-ray diffraction, Dynamic light scattering, Zeta potential, Transmission electron microscopy and Field emission scanning electron microscopy analysis revealed stable, uniform distribution, spherical shape and crystalline nature of POAuNPs with a size range of 3-46 nm. Furthermore, the POAuNPs potentially inhibited the growth of pathogenic bacterial strains<i>Escherichia coli</i>and<i>Staphylococcus aureus</i>. The synthesized POAuNPs have shown potential antioxidant effects against 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and nitric oxide (NO) radical scavenging assays with an EC₅₀value of 8.875 ± 0.082, 52.593 ± 2.506 and 43.717 ± 1.449 µg mL^-1, respectively. Moreover, the value of EC₅₀for the total antioxidant capacity of POAuNPs was found to be 23.667 ± 1.361 µg mL^-1. The cell viability of human breast cancer cells, MDA-MB-231 and MCF-7, was found to be reduced after treatment with POAuNPs, and IC₅₀values were found to be 19.753 ± 0.640 and 35.035 ± 0.439 µg mL^-1, respectively. Further,<i>in vitro</i>biochemical assays revealed that POAuNPs induces metabolic reprogramming in terms of reduced glucose uptake, increased lactate dehydrogenase (LDH) release and, disruption of oxidative balance through depletion of glutathione levels, increased nitric oxide (NO) and lipid peroxidation levels as a possible pathway to suppress human breast cancer cell proliferation. Apoptosis-specific nuclear modulations induced by POAuNPs in human breast cancer cells were validated through 4',6-diamidino-2-phenylindole (DAPI) nuclear staining. The present investigation thus attempts to show the first ever fabrication of AuNPs using an aqueous extract of<i>P. oxalicum</i>associated with<i>A. rohituka</i>. The results revealed unique physico-chemical characteristics of mycogenic AuNPs, and screening their effect against breast cancer via metabolic reprogramming and induction of apoptosis thus adds great significance for cancer therapeutics, suggesting further exploration to develop nanotherapeutic drugs.