Phytochemical-Driven Selenium Nanoparticles from Tribulus terrestris: A Multi-Mechanistic Antifungal and Anti-Aflatoxigenic Strategy with Biocompatibility

• Selenium nanoparticles were synthesized using Tribulus terrestris leaf extract (TT-SeNPs). • TT-SeNPs showed antifungal activity through spore germination, ROS induction, membrane disruption and aflatoxin B1 suppression in A. flavus • TT-SeNPs showed selective toxicity towards cancer cells while maintaining safety in non-cancerous cells. • TT-SeNPs exhibited no developmental toxicity in zebrafish embryos at lower dose and found biocompatible. • TT-SeNPs is potential safe for food preservation and post-harvest management. Sustainable strategies for controlling aflatoxigenic fungi and their toxins are urgently needed to ensure food safety and reduce post-harvest losses. In this study, selenium nanoparticles were biosynthesized using Tribulus terrestris leaf extract (TT-SeNPs) and evaluated for their antifungal and antimycotoxigenic efficacy against Aspergillus flavus . Phytochemical profiling of the T. terrestris leaf extract by LC–MS/MS-QTOF revealed presence of gallic acid, epicatechin, acacetin, apigenin, chrysoeriol, quercetin, and kaempferol glycosides, which served as natural reducing and stabilizing agents during nanoparticle synthesis. The biosynthesized TT-SeNPs exhibited a characteristic UV–visible absorption peak at 328 nm, spherical morphology with sizes ranging from 60–105 nm, a highly negative zeta potential (−44 mV), and predominantly amorphous structural features confirmed by XRD and Raman analyses. The TT-SeNPs exhibited potent antifungal activity against Aspergillus flavus, with minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations of 28.56 ± 5.91 and 43.19 ± 7.84 µg/mL, respectively. The TT-SeNPs significantly suppressed spore germination, reduced mycelial biomass, and markedly inhibited aflatoxin B1 production in a dose-dependent manner. Mechanistic investigations revealed elevated intracellular reactive oxygen species generation, depletion of ergosterol content, and disruption of membrane integrity, indicating multi-targeted interference with fungal physiology. Cytotoxicity assays demonstrated selective toxicity toward MDA-MB-231 cancer cells, with minimal effects on HEK-293 non-cancerous cells, supporting the inherent redox-modulating behavior of the SeNPs. The safety assessment showed that TT-SeNPs exhibited low developmental toxicity in zebrafish embryos up to 100 µg/mL, with confirmed biocompatibility at biologically relevant concentrations. Overall, this study demonstrates that phytochemically capped TT-SeNPs function as a multi-mechanistic antifungal and anti-aflatoxigenic agent with favorable biocompatibility. The findings highlight their potential application as a sustainable, plant-derived nanotechnology platform for food preservation, crop protection, and safe post-harvest management of A. flavus contamination.