Fabrication of Enzyme-Responsive Prodrug Self-Assembly Based on Fluazinam for Reducing Toxicity to Aquatic Organisms

Prodrug-based nanodrug delivery systemswere drug formulationsby covalently conjugating drugs with inversely polar groups via acleavable bond to self-assemble into nanoparticles for efficient drugdelivery. To improve the utilization efficiency of fluazinam (FZN),enzyme-responsive prodrugs were prepared by conjugating FZN with differentalkyl aliphatic acids through a nucleophilic substitution reactionand subsequently self-assembled into nanoparticles (FZNP NPs) withoutusing any harmful adjuvant. The obtained FZNP NPs exhibited excellentefficacies against Sclerotinia sclerotiorum as a result of improved physicochemical properties, including lowsurface tension, high retention, and enhanced photostability. TheLC(50) values of FZNP NPs toward zebrafish were 3-8times that of FZN, which illustrated that the FZNP NPs reduced thedetriments of FZN to the aquatic organisms while retaining good biologicalactivity. Therefore, prodrug self-assembly technology would offera potential method for improving the utilization efficiency of pesticidesand lowering the risks to the ecological environment.