A nanoformulation that enhance the efficiency of camptothecin against lepidopteran pests by controlled release and ‘poison bait’ strategies

Pesticides are critical to securing crop yields, but the extremely low utilization of conventional pesticides puts a serious strain on human development and the environment. Natural product pesticides meet the needs of sustainable development, but challenges like high costs and slow efficacy hinder their widespread use. Camptothecin (CPT) is a natural product with potent bioactivity for various insect pests, but its bioactivity for lepidopteran pests is limited due to the ring-opening in their alkaline midgut. To enhance CPT's efficacy, a nanopesticide CPT@Zein-FA, which consists of the plant-derived zein and ferulic acid (FA), was designed and verified to be able to improve the bioactivity of CPT against lepidopteran pests including Ostrinia furnacalis, Spodoptera frugiperda and Mythimna separata. The nanopesticide CPT@Zein-FA approximately 100 nm in size, exhibited uniform dispersion, strong adhesion, and stability. CPT@Zein-FA utilizes pH and redox dual response mechanisms to achieve protection in the midgut environment and release in the hemocoel/intracellular environment. With the help of zein bait, CPT@Zein-FA can also promote the feeding of insects and accelerate their death. Metabolomic analysis revealed CPT's lethal impact on insect metabolism by inhibiting nucleotide synthesis, disrupting body size and development through lipid metabolism and insect hormone synthesis inhibition. This work provides new ideas for the large-scale application of natural product pesticides and contributes to the sustainable development of the world.