Construction of phenothiazine-decorated ZnO quantum dots with intelligent response to bacterial pH/amidase microenvironment for inducing bacterial ferroptosis-like death

Abstract

Growing antimicrobial resistance has become a global crisis for global health and food security. To avoid or reduce antimicrobial resistance, stimuli-responsive materials are becoming advanced and multifunctional tools for fighting against microbial infection. In this study, a smart nanocarrier, namely ZnO QDs-PTZ (phenothiazine-decorated ZnO quantum dots), was designed by means of organic–inorganic hybridization. The mechanistic study of ZnO QDs-PTZ nanocarrier were made by electron microscope and transcriptome sequence analysis, implied that it was capable of responding to bacterial pH/amidase microenvironments, and could trigger a synergistic bactericidal effect though bacterial ferroptosis-like death induced by iron enrichment, cell membrane damage by lipid peroxidation, and glutathione depletion. Further, the designed nanocarrier demonstrated high water dispersibility, foliar wettability, and good absorption behavior in plants, resulting in excellent assay outcomes in vitro [ZnO QDs-PTZ A with minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC) values of 12.5 and 18.8 μg mL⁻¹] and in vivo (curative effectiveness: 66.3 %; protective effectiveness: 65.5 %). Additionally, their non-toxic characteristics were verified in rice seedling germination, rice plants, and zebrafish. Overall, this study proposes an antibacterial substitute constructed by phenothiazine and ZnO quantum dots via ferroptosis-like death-inducing/membrane-targeted synergistic bactericidal effects, which may provide a foreground for controlling intractable bacterial infection, and also provides new insights into the potential of organic–inorganic hybrid nanomaterials characterized by safe, pH/amidase-responsive release ability.