Precision Dosing of Antibiotics and Potentiators by Hypoxia-Responsive Nanoparticles for Overcoming Antibiotic Resistance in Gram-Negative Bacteria.

The stalling development of antibiotics, especially against intrinsically resistant Gram-negative pathogens associated with outer membranes, leads to an emerging antibiotic crisis across the globe. To breathe life into existing drugs, we herein report a hypoxia-responsive nanoparticle (NP) that encapsulates a hydrophobic antibiotic, rifampicin, and a cationic potentiator, polysulfonium. The simultaneous release of antibiotics and potentiators can be promoted and inhibited in response to the severity of bacterial-induced hypoxia, leading to antimicrobial dosing in a precision manner.