Multifunctional metal-phenolic nanoparticles with antibacterial and anti-inflammatory effects for osteomyelitis management.

Abstract

Osteomyelitis is a serious inflammatory disease mostly caused by bacterial infections. It is necessary to simultaneously eradicate bacterial cells and inhibit inflammation in treating osteomyelitis. Herein, we design an innovative zinc ion (Zn²⁺)-based nano delivery system for the management of osteomyelitis. Taking advantage of the coordination self-assembly of Zn²⁺, quercetin (QU), and ε-poly-L-lysine (EPL), Zn²⁺-containing nanoparticles (denoted as ZQE NPs) are prepared. ZQE NPs are spherical nanoparticles with amorphous structures. They are stable in the physiological neutral environment but can be dissociated in an acidic microenvironment of infection sites. Since Zn²⁺ is encapsulated into ZQE NPs by coordination interaction, the deactivation of Zn²⁺ by proteins can be effectively avoided. Therefore, ZQE NPs can maintain excellent bactericidal activity in a protein-rich environment, while dissociative Zn²⁺ doesn't exhibit obvious bactericidal ability. Meanwhile, ZQE NPs are highly effective at scavenging intracellular reactive oxygen species (ROS) and inhibiting pro-inflammatory cytokines, due to the strong anti-inflammatory effects of QU and Zn²⁺. The in vivo therapeutic efficacy of ZQE NPs is assessed using a rat model of methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. Results demonstrate that ZQE NPs effectively eradicate bacterial cells and reduce inflammation in vivo, thereby promoting osteogenesis and recovery of osteomyelitis.