Antimicrobial Honey-Inspired Glucose-Responsive Nanoreactors by Polymerization-Induced Self-Assembly

The rise of antimicrobial resistance is at the forefront of global healthcare challenges, with antimicrobial infections on track to overtake cancer as a leading cause of death by 2050. The high effectiveness of antimicrobial enzymes used in combination with the protective, inert nature of polymer materials represents a highly novel approach toward tackling microbial infections. Herein, we have developed biohybrid glucose oxidase-loaded semipermeable polymersome nanoreactors, formed using polymerization-induced self-assembly, and demonstrate for the first time their ability to "switch on" their antimicrobial activity in response to glucose, a ubiquitous environmental stimulus. Using colony-counting assays, it was demonstrated that the nanoreactors facilitate up to a seven-log reduction in bacterial growth at high glucose concentrations against a range of Gram-negative and Gram-positive bacterial pathogens, including a methicillin-resistant Staphylococcus aureus clinical isolate. After demonstrating the antimicrobial properties of these materials, their toxicity against human fibroblasts was assessed and the dosage of the nanoreactors further optimized for use as nontoxic agents against Gram-positive bacteria under physiological blood glucose concentrations. It is envisaged that such biohybrid nanomaterials will become an important new class of antimicrobial biomaterials for the treatment of bacterial infections.