Nanoparticles co-delivering double-stranded RNA and insecticide enhance control efficacy and overcome pest resistance

Chemical insecticides are essential in controlling agricultural pests. The emergence of resistance leads to control failures, thus developing strategies to delay the evolution of resistance while effectively managing is crucial for sustainable pest control. The development of RNA interference (RNAi) and nano-insecticides has introduced novel strategies for controlling pests, yet the synergistic application of these technologies in insecticide resistance management remains to be empirically validated. In this study, the enhancing control efficacy and dsRNA uptake efficacy through formulation with the nano-carrier, aminated mesoporous organosilica nanoparticles (MON-NH 2 ), is reported in Cydia pomonella . Following the amination process and modifications, the nanoparticles are thoroughly characterized. Delivery of lambda -cyhalothrin (LCT) with MON-NH 2 increased the susceptibility of both laboratory-selected and field-evolved resistant populations of C. pomonella and orchard control efficacy. Moreover, the efficiency of RNAi of MON-NH 2 -dsRNA targeting resistance-related cytochrome P450 genes ( CpCYP9A120 , CpCYP9A121 , and CpCYP9A122 ) was significantly enhanced compared to naked dsRNA. Furthermore, bioassays showed that utilizing MON-NH 2 for co-delivery of dsRNA of these P450 genes and LCT significantly increased the susceptibility of C. pomonella -resistant populations against LCT. Orchard trials further confirm the effectiveness of the delivery system in improving control efficacy and overcoming resistance in C. pomonella field populations and its versatility in controlling other fruit borers. Additionally, these nano-carrier co-delivery complexes pose non-target biosafety to enemies, pollinators, and a model organism. Our findings hold significance for implementing lepidopteran pest controlling using RNA-based products, offering options for resistance management in sustainable pest control strategies with currently available insecticides resistant to pest populations. • MON-NH 2 enhances the susceptibility of Cydia pomonella to lambda -cyhalothrin (LCT). • LCT@MON-NH 2 improves orchard control efficacy against other fruit borers. • RNAi efficacy of MON-NH 2 @dsCpCYP9As is significantly enhanced. • LCT@MON-NH 2 @dsCpCYP9As overcome the resistance of C. pomonella to LCT. • The co-delivery complexes pose high biosafety to non-target insects.