A macrophage-like biomimetic nanoparticle with high-efficiency biofilm disruption and innate immunity activation for implant-related infection therapy

The innate immune system's inactivation and microbial biofilm-induced antibiotic resistance are the main causes of implant-associated infections (IAIs), which frequently result in implant surgical failure. Refractory recolonization is the consequence of standard therapies that are unable to consistently suppress escaping planktonic bacteria from biofilm, thereby enabling IAIs to thrive. Here, we specifically designed a macrophage-like biomimetic nanoparticle (F/R@PM) for a biofilm microenvironment (BME), which was fabricated by coating the cell membrane derived from macrophage onto poly (lactic-co-glycolic acid) (PLGA) namoparticles (NPs) loaded with FOT (NO donor) and R837 (TLR7 agonist). After injecting F/R@PM into mice with implant-associated infections, it was able to selectively target macrophages through macrophage membrane proteins on its surface and effectively release FOT and R837. Then, FOT that spreads outside the cell could react with glutathione (GSH) in the BEM to rapidly produce a large amount of NO inside biofilms to destroy the biofilm and kill bacteria. At the same time, R837 would encourage macrophages to scavenge planktonic bacteria that had escaped biofilm disintegration through improved phagocytosis. Overall, this work shows that NO treatment and immunotherapy together have promising potential for the long-term and efficient control and eradication of IAIs.