Differential ecotoxicity of nanoencapsulated metamifop and its active ingredient in zebrafish (Danio rerio): Insights from transcriptome and metabolome analysis.

Nanopesticides have gained increasing attention for their enhanced control efficacy. However, their potential toxicity to environmental and public health remains largely unexplored, and their toxicological mechanism at molecular level is poorly understood. To this context, a hydrophilic and lipophilic diblock polymer (HLDP) was designed and synthesized to develop a novel nanoherbicide metamifop (MP)@HLDP with high herbicidal activity against barnyard grasses (Echinochloa crusgalli). Using zebrafish (Danio rerio) as a model organism, this study evaluated the toxicological effects and molecular mechanisms of MP@HLDP. Compared to MP alone, MP@HLDP displayed fewer negative impacts on the hatchability, malformation, survival and cell apoptosis of zebrafishes. Combined transcriptome and metabolome analysis revealed that MP@HLDP could modulate key detoxification pathways, including the cytochrome P450 system, by down-regulating the expression of genes involved in xenobiotic metabolism such as ugt1a7, ugt2a4, gstp2, etc. Additionally, MP@HLDP exposure significantly increased the accumulation of various metabolites, such as hydrocortisone in zebrafish larvae. These changes resulted in lower oxidative damage, reduced GST and caspase-3 activities, and diminished metabolic burden in zebrafish embryos. These findings suggest that MP@HLDP can not only provide enhanced herbicidal activity, but also mitigate the developmental toxicity of MP, making it a promising approach for safer herbicide application in agricultural systems.