Fabrication of Enzyme-Responsive Prodrug Self-Assembly Based on Fluazinam for Reducing Toxicity to Aquatic Organisms
Xiaohong Zhang, Gang Tang, Zhiyuan Zhou, Huachen Wang, Xuan Li, Guangyao Yan, Yulu Liu, Yuqi Huang, Jialu Wang, Yongsong Cao
Abstract
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 LC 50 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.