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

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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 (EC 50 = 3.1 μg/mL) against Rhizoctonia solani than pure azoxystrobin (EC 50 = 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 (EC 50 = 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.