Phase separation of extracellular polymeric substances induced by bacteria responsive Nano-Antibiotics for drug-resistant bacterial infection management

Bacterial quorum sensing (QS) and bacterial extracellular polymeric substances (EPS) are the major challenges in treating biofilm chronic infection. Herein, we proposed targeting intervention phase separation of EPS by nanoantibiotics (Ir(ppy)2dmb-PAZ-HA) as an effective strategy for combating bacterial biofilm infection, in which Iridium complex (Ir(ppy)2dmb-CHO) and antibiotic (Pazufloxacin, PAZ) for synergistic antibacterial, and hyaluronic acid (HA) was used to enhance Ir(ppy)2dmb-PAZ release on-demand in biofilm microenvironment. In vitro results showed that Ir(ppy)2dmb-PAZ-HA holds excellent antibacterial activity and antibiofilm capacity. Importantly, Ir(ppy)2dmb-PAZ-HA can be target to regulate phase separation of EPS, and then interfere with biofilm formation, which is a competitive mechanism between Ir(ppy)2dmb-PAZ-HA and Methicillin-resistant Staphylococcus aureus (MRSA) itself. In addition, in vivo results confirmed that Ir(ppy)2dmb-PAZ-HA was able to accelerate biofilm chronic wound healing, and effectively alleviate bacterial acute lung infection. Accordingly, this study provides a new antibiofilm target, and provides a novel idea for the design of small molecular metal antibacterial drugs and antibiotic reuse.