Figure 1.

pH-controlled assembly/disassembly strategy for the fabrication of biofilm-responsive nanoantibiotics (rAgNAs) to enhance the treatment of biofilm-associated infections. (a) rAgNAs with high colloid stability and negative charge are supposed to circulate for a long time in vivo. (b) Once in the acidic microenvironment of the biofilm, the rAgNAs go through charge reversal triggered by the protonation of the imidazole groups and tend to accumulate in the biofilm area owing to the electrostatic interaction. (c) Increased electrostatic repulsion consequently leads to disassembly, and a size transition takes place, which is beneficial to the enhanced penetration of the biofilm. (d) Silver ion leaching can be tremendously accelerated from the surface of the disassembled nanoantibiotics in the acidic microenvironment, and thus rAgNAs are able to exhibit locally amplified bactericidal effects.