COF ‐ PEI ‐ PEG nanocarriers enhance dsRNA delivery to improve RNAi ‐based insect pest control

BACKGROUND: Foliar application of RNA interference (RNAi)-based products offers a promising strategy for protecting crops against insect pests. This approach involves the direct spraying of exogenous double-stranded RNA (dsRNA) to silence specific target genes in pests. However, its practical efficacy is constrained by the environmental degradation of the dsRNA, rapid degradation by gut nucleases, inefficient cellular internalization and limited endosomal escape. The integration of nanotechnology with RNAi has emerged as a promising frontier in sustainable pest control, offering improved dsRNA stability, enhanced cellular delivery, and the potential to reduce conventional pesticide use. In this study, we explored the use of a positively charged covalent organic framework (COF)-based nanocarrier functionalized with polyethylenimine (PEI) and polyethylene glycol (PEG) for dsRNA delivery. RESULTS: The resulting COF-PEI-PEG@dsRNA complexes effectively resisted degradation by nuclease-rich midgut extracts. Moreover, COF-PEI-PEG facilitated efficient dsRNA delivery into Drosophila S2 and Lepidopteran Sf9 cells, resulting in significant improvement in target gene knockdown. In vivo, COF-PEI-PEG@dsRNA significantly enhanced RNAi efficacy in Leptinotarsa decemlineata and Drosophila suzukii, although no improvement was observed in Spodoptera exigua. CONCLUSION: Collectively, our findings highlight the potential of COF-PEI-PEG as effective dsRNA delivery platforms, offering a novel and versatile tool to enhance RNAi-based insect management and fundamental entomological research. © 2026 Society of Chemical Industry.