Self-assembled co-delivery nanoplatform for increasing the broad-spectrum susceptibility of fall armyworm toward insecticides

Unscientific application of insecticides has led to severe resistance of pests to almost all classes of insecticides. Enhanced detoxification is the most common mechanism for this kind of resistance. Object: Fall armyworm (FAW) has developed insecticide resistance, which is often linked to the overexpression of detoxification genes. Herein, a multicomponent nano-pesticide is designed to increase its broad-spectrum susceptibility toward insecticides. Regulatory function of nuclear factor erythroid 2-related factor 2 (Nrf2) in detoxification was confirmed using transcriptome sequencing, quantitative real-time PCR and enzyme activity measurement. A star polycation (SPc) was adopted to construct the pesticide/SPc/complex, whose self-assembly mechanism and characterization were examined using isothermal titration calorimetry, dynamic light scattering and transmission electron microscope. The delivery efficiency of SPc-loaded dsRNA was examined in vitro and in vivo using fluorescent tracer technique. A multicomponent nano-pesticide was created through the integration of bacterial expression system and nano-delivery system, and its bioactivity was tested in laboratory and field. We confirmed the crucial role of Nrf2 in regulating the detoxification in FAW, and silencing Nrf2 could decrease detoxification gene expression and increase insecticide susceptibility. We then applied the SPc to self-assemble a nanoplatform for delivering Nrf2 double-stranded RNA (dsRNA) and pesticide simultaneously. Nano-sized pesticide/SPc/dsRNA complex exhibited high delivery efficiency in vitro and in vivo. Excitingly, the insecticidal activities of pesticide/SPc/dsNrf2 complexes were remarkably improved with the normalized synergistic ratios of 5.43-6.25 for chlorantraniliprole, 4.45-15.00 for emamectin benzoate, and 6.75-15.00 for spinetoram. Finally, we developed a multicomponent nano-pesticide (pesticide/SPc/dsNrf2 complex) using a bacterial expression system and nano-delivery system. This approach exhibited excellent leaf protection and pest control efficacy. The integration between the pesticide nanometerization and insecticide susceptibility improvement offers a promising strategy to increase insecticidal activity. Our study provides a revolutionary and universal strategy to increase insecticidal activity and decease application doses.