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

Prodrug-based nanodrug delivery systems were drug formulations by covalently conjugating drugs with inversely polar groups via a cleavable bond to self-assemble into nanoparticles for efficient drug delivery. To improve the utilization efficiency of fluazinam (FZN), enzyme-responsive prodrugs were prepared by conjugating FZN with different alkyl aliphatic acids through a nucleophilic substitution reaction and subsequently self-assembled into nanoparticles (FZNP NPs) without using any harmful adjuvant. The obtained FZNP NPs exhibited excellent efficacies against Sclerotinia sclerotiorum as a result of improved physicochemical properties, including low surface tension, high retention, and enhanced photostability. The LC₅₀ values of FZNP NPs toward zebrafish were 3-8 times that of FZN, which illustrated that the FZNP NPs reduced the detriments of FZN to the aquatic organisms while retaining good biological activity. Therefore, prodrug self-assembly technology would offer a potential method for improving the utilization efficiency of pesticides and lowering the risks to the ecological environment.