From De Novo Conceived Small Molecules to Multifunctional Supramolecular Nanoparticles: Dual Biofilm and T3SS Intervention, Enhanced Foliar Affinity, and Effective Rice Disease Control

Abstract Conventional antimicrobials typically exhibit suboptimal deposition on rice leaves, resulting in poor efficacy, further impaired by biofilms and Type III Secretion Systems (T3SS). Herein, this study presents a supramolecular strategy to fabricate BtP27@ β ‐CD, a sunflower‐like material engineered through host‐guest recognition between de novo designed molecule BtP27 and β ‐cyclodextrin. BtP27@ β ‐CD manifests enhanced foliar affinity and in vivo efficiency, demonstrating superior protective (62.67%) and curative (51.16%) activities against bacterial leaf blight at a low‐dose of 200 µg mL −1 compared to commercial thiodiazole‐copper (37.78%/38.13%) without compromising safety. This multifunctional material, structurally derived from dufulin, inherit progenitor's systemic and conductive properties, alongside the capacity to activate salicylic acid‐mediated plant defense pathways. Moreover, it is endowed with the anticipated abilities to disorganize biofilm barriers, annihilate encased pathogens, and inhibit T3SS. This constitutes the inaugural report of a supramolecular‐based biofilm/T3SS dual inhibitor. An expanded investigation into substrate and indication screening identified additional molecules that self‐assemble with β ‐cyclodextrin to form supramolecular materials, exhibiting superior potency against other rice diseases, with protective potency ranging from 63.53% to 73.30% and curative efficacy spanning 42.18% to 60.41% at 200 µg mL −1 . In brief, this work establishes a paradigm for designing guest molecules from scratch to construct supramolecular materials with tailored characteristics.