Modified Betaine as a Mitochondria-Accumulating Ligand for Improving the Succinate Dehydrogenase Inhibitor Fungicide Performance

Abstract Low bioavailability and resistance limit the sustainable application of succinate dehydrogenase inhibitor (SDHI) fungicides. Here, we report a nanofungicide (Flu@DMSNs-NH2@CMC-Bet, FDCB) to promote mitochondrial accumulation, in which fluxapyroxad (Flu) is encapsulated in amino-functionalized dendritic mesoporous silica nanoparticles coated with a carboxymethyl chitosan-betaine (CMC-Bet) shell. FDCB exhibited potent antifungal activity against Curvularia lunata, maintaining 92% inhibition at 0.5 mg·L–1 on day 5 and providing superior control of corn leaf spot than the Flu suspension concentrate (81.1% vs. 46.2%). Fluorescence colocalization analysis revealed preferential accumulation of FDCB in pathogen mitochondria. Compared with Flu alone, FDCB more effectively inhibited succinate dehydrogenase activity, disrupted mitochondrial membrane potential, reduced adenosine triphosphate production, and impaired mitochondrial function. Moreover, FDCB exhibited no detectable phytotoxicity toward corn seedlings and reduced acute toxicity in zebrafish. These findings demonstrate the potential of modified betaine as a quaternary ammonium-based ligand for enhancing mitochondrial accumulation and improving SDHI fungicide performance.