Year: 2025
Type: article
Abstract: IntroductionNanoparticles (NPs) are ultrafine particles that are 1-100 nm.Because of their physical and chemical properties resulting from their small size, they are welcomed as medical or biological application [1,2].Most NPs are considered suitable for drug delivery and treatment because they are the proper size to interface biomolecules, such as DNA and proteins [3][4][5].In particular, their high surface-to-volume ratio allows for enhanced interaction with cellular components, improving drug loading efficiency and targeted delivery [6].Additionally, their tunable surface chemistry enables functionalization with ligands, antibodies, or therapeutic agents, making them highly adaptable for biomedical applications.Various types of NPs, including metal, polymeric, and lipid-based nanoparticles, have been developed to optimize biocompatibility and therapeutic potential [7].Among metallic nanoparticles, gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have attracted significant attention.AuNPs are employed in various biomedical fields, such as diagnosis, cancer treatment, and nanobiotechnology based on their low toxicity and ability to regulate membrane penetration [8,9].For example, in mammalian cancer cells, AuNPs are known to significantly reduce cell viability, which not only inhibit cell proliferation, but also cause cell-cycle arrest [10,11].Additionally, this nanomaterial is also regarded as a potential anticancer agent because it induces cell death, such as apoptosis and necrosis depending on time and concentration [12,13].Furthermore, several papers have reported that AuNPs form a complex with antibiotics to exhibit synergistic effects or enhance the antimicrobial effect while acting as antibiotic carriers [14][15][16].Many studies have found that AuNPs exhibit activity in bacteria, which are mechanisms to repress protein activity and weaken DNA replication.However, mechanisms for anti-yeast or anti-fungal activity require further exploration [17,18].Recently, a novel form of regulated cell death (RCD) distinct from apoptosis and autophagy has been identified.This process, called "ferroptosis," was first described by Dixon et al. in 2012 [19].Unlike previously known RCD mechanisms, ferroptosis exhibits unique morphological features, including the disappearance of mitochondrial Ferroptosis, a novel form of regulated cell death (RCD), has emerged as a promising therapeutic strategy for cancer treatment.While gold nanoparticles (AuNPs) are known to induce cell death and ferroptosis in combination with certain antibiotics, the mechanisms underlying ferroptosis in microorganisms remain poorly understood.This study aimed to investigate whether AuNPs induce ferroptosis-like cell death in the eukaryotic microbe Saccharomyces cerevisiae.Our findings revealed that AuNPs significantly reduced cell viability in S. cerevisiae, suggesting their ability to trigger cell death.Ferroptosis-related precursors, including intracellular iron overload and depletion of glutathione (GSH), were observed, leading to the inactivation of glutathione peroxidase (GPx).These changes were associated with the accumulation of reactive oxygen species (ROS) and lipid peroxidation, which amplified oxidative stress within the cells.Elevated ROS levels and lipid peroxidation further resulted in membrane rupture and the formation of 8-hydroxydeoxyguanosine, indicating DNA damage.Mitochondrial dysfunction, a hallmark of ferroptosis, was also evident.AuNP treatment caused mitochondrial membrane potential hyperpolarization and a reduction in mitochondrial membrane density.Unlike previously characterized forms of RCD, ferroptosis-like death in S. cerevisiae did not involve chromatin condensation, DNA fragmentation, or metacaspase activation.Finally, ferroptosis-like characteristics were confirmed using Liperfluo, a lipid ROSspecific probe.In conclusion, this study demonstrated that AuNPs can induce ferroptosis-like cell death in S. cerevisiae.These findings highlight the potential of AuNPs as antifungal agents and contribute to the broader understanding of ferroptosis in eukaryotic microbes.
Authors: Min Seok Kwun, Dong Gun Lee
Institution: Kyungpook National University
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: bronze
Award: G1806242956
OpenAlex ID: W4409876175