Constructing co-assembly derived smart lipid nanoparticles for enhanced antimicrobial potency with plant growth-promoting potential

Lipid nanoparticles (LNP) are widely used in biomedical applications due to their biocompatibility and safety, yet their translation to plant systems remains limited. Here, we establish a unified strategy integrating antibacterial compound discovery, plant-adapted nanocarrier design, and mechanistic elucidation to combat bacterial plant diseases. A series of thymol-derived quaternary ammonium compounds were synthesized, among which C2 was identified as the lead candidate with potent antibacterial activity (EC₅₀ = 0.78 µg/mL). Upon co-assembly into lipid nanoparticles, C2@LNP exhibited pH-responsive release under infection-associated acidic conditions and achieved a high drug-loading efficiency of 82.41%. This plant-tailored LNP system enhances cuticle penetration and foliar retention, as demonstrated by systematic analyses of leaf deposition, droplet behavior, and microscopic adhesion. Consequently, C2@LNP enabled improved disease control at reduced dosages, with protective and curative efficacies 1.94-fold and 1.56-fold higher than those of free C2, respectively. Interestingly, certain lipid components of the nanocarrier, particularly HSPC, exhibited a preliminary plant growth-promoting potential. Mechanistic studies indicated that the enhanced antibacterial performance arises from suppression of quorum sensing, membrane disruption, and induction of apoptosis-like cell death. Overall, this work establishes a sustainable pesticide delivery paradigm for environmentally friendly crop protection.