Towards minimal-excipient agrochemicals: polymorphic nanocrystals maximize efficacy and biosafety for crop protection

The widespread reliance on synthetic pesticides for global food production is compromised by poor water solubility and inefficient delivery, resulting in substantial off-target losses and low utilization efficiency of applied active ingredients. While nanopesticides offer potential solutions, their carrier-dependent architectures often introduce cost, complexity, and ecological uncertainties that run counter to sustainability principles. Here we report a carrier-minimized paradigm that redefines pesticide formulation through molecular engineering. We synthesize the first polymorphic nanocrystals of chlorantraniliprole (CAP) with high active content (92.6% amorphous, CAP NC-1; 86.5% crystalline Form I, CAP NC-2). Both nanocrystals show enhanced dissolution, leaf wetting and deposition. We demonstrate that particle size reduction appears to contribute more strongly to enhanced insecticidal activity, whereas the metastable amorphous form primarily improves solubility. Transcriptomic analysis reveals varied gene expression patterns between the two nanocrystal formulations, with both treatments broadly activating cuticle-related and detoxification-associated pathways, albeit with differing relative enrichment. Amorphous nanocrystals are associated with stronger upregulation of cuticle protein genes, while crystalline nanocrystals show more pronounced induction of detoxification-related transcripts. Critically, this performance gain is achieved without increasing toxicity to non-target plants, aquatic organisms, or mammalian cells. This study establishes a high-loading nanocrystal model system that enables systematic decoupling of particle size and solid-state effects, providing correlative insights into the structure–property–performance relationships of agrochemical nanocrystals. Our findings offer a foundation for the development of next-generation crop protection technologies that align high efficiency with environmental and food system sustainability.