Multifunctional phytochemical nanoplatform for comprehensive treatment of all-stage MRSA biofilm associated infection and its accompanying inflammation

The acquired drug resistance coupled with complex physiology and pathogenesis of biofilm challenges multidrug-resistant bacterial biofilm infection treatment. Herein, antimicrobial phytochemical isoliquiritigenin (ISL) loaded rhamnolipid (RL) modified chitosan nanoparticles (ISL@RL-CS) were constructed. The obtained ISL@RL-CS NPs were able to simultaneously eradicate methicillin-resistant Staphylococcus aureus (MRSA) biofilms at all stages and relieve accompanied inflammation. In the acid environment of biofilms, RL could be detached from the ISL@RL-CS and destroyed the biofilm structure. Then, the combination of phytochemical ISL and cationic chitosan could rapidly kill the dispersed bacteria, and inhibit the re-adhesion of residual bacteria, thus preventing the re-formation of new biofilms. Additionally, the inflammatory responses at the infection site were simultaneously alleviated by the anti-inflammatory features of ISL. In the MRSA-biofilm implant infected mice model, ISL@RL-CS demonstrated prominent biofilm eradication and anti-inflammation efficacy. Taken together, ISL@RL-CS with simple formulation but multi-functions provides a comprehensive and sustainable strategy for managing the intractable MRSA biofilm infections.