A double-enzyme cascade-responsive nanohydrogel for activable photodynamic antibacterial therapy and dual fluorescence signal detection of bacterial infections

The tremendous morbidity and mortality caused by bacterial infections have emerged as a formidable menace to human health. The early detection and treatment of bacterial infections is imperative for effectively managing the progression of infectious diseases and mitigating infection-related mortality. In this study, we constructed a nanohydrogel consisting of cationic zinc phthalocyanine (CZP) and hyaluronic acid, which was further functionalized with a novel β-galactosidase detection probe, resulting in the formation of product CZP@HA:probe. The release of CZP and probe from CZP@HA:probe can be triggered by hyaluronidase, and the fluorescence of CZP and probe was turned on successively by hyaluronidase and β-galactosidase, respectively, demonstrating the dual enzyme-responsive property of CZP@HA:probe. CZP@HA:probe exhibited potent photodynamic killing activity against bacteria. The antibacterial mechanism potentially involved the generation of reactive oxygen species within bacteria and the disruption of the bacterial outer membrane. CZP@HA:probe had significant efficacy in promoting wound healing and exhibited a fluorescent indication of wound infections. The construction strategy of the nanohydrogel can be applied to other photosensitizers and probes, offering a novel perspective for the detection and treatment of bacterial infections.