pH-Responsive Fluorescent Polymer-Drug System for Real-Time Detection and In Situ Eradication of Bacterial Biofilms

Bacterial biofilms encased in extracellular polymeric substances to create protected microenvironments are typically challenging to disperse by common antibiotics and cannot be in situ visualized under current modalities. Herein, a pH-responsive branched polymer [poly(MBA-AEPZ)-AEPZ-NA] capable of overcoming antibiotic resistance and real-time visualizing biofilms for fluorescence imaging-guided infection control is reported. The positively charged polymer can effectively penetrate bacterial biofilms, neutralize the anionic character, and then disrupt the structural integrity, thus significantly promoting the transport of antibiotics into biofilms. The polymer shows a weak fluorescence emission intensity under physiological conditions (pH 7.4) but emits intense green-light emission within the localized biofilm microenvironment (pH 5.5) to real-time visualize bacterial biofilms. A therapeutic system made of the polymer and a model antibiotic can significantly reduce the dosages of the drug, thereby minimizing biofilm-induced drug resistance. Notably, a green fluorescent polymer responding to localized pH conditions is demonstrated in living zebrafish. This work confirmed that combinations of the pH-responsive branched polymer and antibiotics could be administered to overcome drug resistance and realize fluorescence imaging-guided treatment of bacterial biofilm infections.