Multilevel synergistic mechanisms of a nanocarrier-enabled topramezone herbicide against invasive weeds

The rapid proliferation of invasive weeds has emerged as an escalating "major threat", and the inefficient utilization and environmental dispersion of conventional herbicides pose persistent challenges in agricultural production. Herein, an amphiphilic hydrophilic-lipophilic diblock polymer (HLDP) was constructed to develop a nano-enabled topramezone (TOP) with excellent herbicidal performance toward invasive weed Cyclachaena xanthiifolia while reducing ecological risk. The HLDP displayed a high loading content of 46.22% toward TOP, and the dynamic self-assembly was spontaneously driven by hydrophobic association and hydrogen bonding, characterized by isothermal titration calorimetry, molecular docking/dynamics simulation and Fourier transform infrared spectroscopy. The encapsulation within HLDP decreased the particle size of TOP down to 102 nm to form stable spherical particles with the zeta potential of 30.13 mV, and the thermal stability of TOP was significantly improved by forming a hybrid nanostructure. Compared to free TOP, the TOP@HLDP exhibited excellent foliar behavior with reduced contact angle (1.4-fold), enhanced spray retention (2.3-fold), and increased systemic uptake (2-fold), as well as altered soil transport behavior. Notably, both laboratory and field trials demonstrated significantly enhanced herbicidal activity of TOP@HLDP compared with free and commercial formulations, resulting in stronger growth inhibition and reduced chlorophyll and nitrogen contents. Integrated transcriptomic and metabolomic analyses revealed that the complexation with HLDP further induced amplified oxidative and hormonal stress, characterized by suppressed photosynthetic electron transport, impaired NADPH generation, redirected carbon allocation, and enhanced jasmonic acid biosynthesis, which was consistent with the physiological responses in invasive weeds. Moreover, biosafety assessments confirmed the superior biocompatibility of TOP@HLDP toward non-target organisms, including fruit flies, S2 cells and maize seeds. Collectively, our study extensively elucidated the multiple synergistic mechanisms underlying the HLDP-based delivery system from dynamic self-assembly to multi-omics basis, offering a reliable strategy for designing/developing nano-herbicides with high bioactivity and excellent biocompatibility toward invasive weeds.