A biomimetic nano-NET strategy for the treatment of MRSA-related implant-associated infection

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has spread across diverse global environments, and MRSA-related infection is a major threat to public health. Implant-associated infection (IAI) caused by MRSA remains a tough global clinical problem. Conventional antibiotic therapy has limited efficacy in treating MRSA-related IAI, and antibiotic abuse has resulted in the emergence of multidrug-resistant bacteria. Hence, there is a necessity to explore more effective approaches to deal with MRSA-related IAI. Herein, inspired by neutrophil extracellular traps (NETs) released by neutrophils to kill microorganisms, this study proposes a novel biomimetic nano-NET strategy using an epsilon-poly-L-lysine-coated CuO₂ nanoplatform, denoted as PCPNAs. The function-adaptive nanoplatform exhibited excellent Fenton-like performance, including robust ROS generation and GSH scavenging ability. PCPNAs showed >90% cell viability in mammalian cells and reduced bacterial burden by 7.65 log₁₀ CFU in vitro. Moreover, the positively charged PCPNAs could easily bind to negatively charged MRSA cells through charge-coupling and simultaneously exerted a trapping effect on MRSA cells. Notably, PCPNAs self-assembled into web-like structures to physically trap and kill biofilm bacteria, achieving 99.58% biofilm eradication. Furthermore, PCPNAs showed satisfactory biocompatibility in vivo and displayed ideal anti-bacterial and anti-inflammatory effects in a mouse model with implant-associated infection. With further development and optimization, the biomimetic nano-NET strategy based on PCPNAs provides a new therapeutic option for the treatment of MRSA-related implant-associated infection.