ZIF-90 nanocarrier enhances antifungal activity of azoxystrobin via zinc-triggered oxidative stress and membrane permeabilization.

Fungicides encapsulated in nanocarriers generally exhibit superior antifungal activity compared to their free counterparts, while the underlying synergistic mechanisms remain unclear. Here, we synthesized azoxystrobin-loaded zeolitic imidazolate framework-90 (Azo@ZIF-90), which showed 36.7% higher antifungal activity (EC50 = 3.1 μg/mL) against Rhizoctonia solani than pure azoxystrobin (EC50 = 4.9 μg/mL). Leaf inoculation assays indicated that Azo@ZIF-90 achieved a 75.2% higher control efficacy against rice sheath blight than azoxystrobin suspension concentrate. The improved performance was attributed to the inherent bioactivity of ZIF-90 (EC50 = 86.6 μg/mL) and the synergistic effect of ZIF-90 and azoxystrobin. Bioassays confirmed that the antifungal action of ZIF-90 mainly originated from zinc ion release. Integrated multi-omics analysis demonstrated that ZIF-90 targeted key biological pathways associated with oxidative stress and transmembrane transport. Biochemical assays further verified that ZIF-90 triggered intracellular reactive oxygen species (ROS) accumulation and subsequent fungal membrane permeabilization. The membrane damage not only endowed a novel antifungal mechanism but also promoted the intracellular uptake of azoxystrobin, enabling the dual-pathway enhancement of azoxystrobin efficacy by ZIF-90. Moreover, ZIF-90 showed good biocompatibility toward rice plants. This work clarified how ZIF-90 boosted the bioactivity of azoxystrobin, offering new insights into the design of high-efficiency green nanofungicides.