Erythrocyte membrane-enveloped molybdenum disulfide nanodots for biofilm elimination on implants via toxin neutralization and immune modulation

Implant-related infections (IRIs) caused by bacterial biofilms remain a prevalent but tricky clinical issue, and are characterized by drug resistance, toxin impairment and immunosuppression. Recently, reactive oxygen species (ROS)- and hyperthermia-based antimicrobial therapies have been developed to effectively destroy biofilms. However, almost all of them have failed to simultaneously focus on the immunosuppressive biofilm microenvironment and bacterial toxin-induced tissue damage. Herein, we proposed a one-arrow-three-hawks strategy to orchestrate hyperthermia/ROS antibiofilm therapy, toxin neutralization and immunomodulatory therapy through engineering a bioinspired erythrocyte membrane-enveloped molybdenum disulfide nanodot (EM@MoS2) nanoplatform. In the biofilm microenvironment, pore-forming toxins actively attack the erythrocyte membranes on the nanodots and are detained, thus staying away from their targets and mitigating tissue damage. Under near-infrared (NIR) laser irradiation, MoS2 nanodots, with superb photothermal and peroxidase (POD)-like properties, exert a powerful synergistic antibiofilm effect. More intriguingly, we initially identified that they possessed the ability to reverse the immunosuppressive microenvironment by skewing the macrophages from an anti-inflammatory phenotype to a proinflammatory phenotype, which would promote the elimination of biofilm debris and prevent infection relapse. Systematic in vitro and in vivo evaluations have demonstrated that EM@MoS2 achieves a remarkable antibiofilm effect. The current study integrated the functions of hyperthermia/ROS therapy, virulence clearance and immune regulation, which could provide an effective paradigm for IRIs therapy.