Incorporation of powerful RNA interference targets within nano-enabled co-delivery platforms for broad-spectrum resistance management.

The continuous escalation of pest resistance leads to the ineffectiveness of most conventional pesticides, which has posed a serious threat to global food security and public health. Metabolic resistance regulated by core detoxification enzymes and penetration resistance mediated by thickened body wall/intestine are the key drivers for resistance evolution. Most existing publications focus on the functional analysis of individual target, which makes it difficult to achieve broad-spectrum resistance management. To this context, this review systematically outlines four key transcription factor-mediated metabolic signaling pathways, and analyzes the mechanism of penetration resistance mediated by body wall/intestinal thickening, aiming to identify effective RNA interference (RNAi) targets for resistance management. Subsequently, this review proposes the design/construction strategy of nano-enabled co-delivery platforms, and elaborates on their synergistic mechanisms compassing stability, foliar adhesion and plant uptake, etc. Finally, this review summarizes the application cases of nano-enabled co-delivery platforms in pest resistance management, and outlines the prospects of this technology, including multi-target coordinated interference, field adaptability improvement, etc. Overall, this work provides abundant synergistic RNAi targets for broad-spectrum resistance management, which is particularly important for design/development of multicomponent RNA nano-pesticides toward global resistant pests.