Iron‐Hijacking Trojan Horse Nanoplatform Combats Implant‐Associated Biofilm Infections Through Immuno‐Fibrotic Remodeling

ABSTRACT Implant‐associated biofilm infections persist due to a vicious cycle of biofilm resilience and fibrosis‐driven immune exclusion. To break this cycle, we engineered a photothermal nanoplatform (CHPB@H) consisting of curcumin‐loaded hollow Prussian blue (CHPB) nanoparticles embedded in an injectable thermosensitive chitosan hydrogel for near‐infrared (NIR)‐triggered local delivery. Upon NIR irradiation, the platform releases iron ions and curcumin that self‐assemble into Fe‐curcumin (Fe‐Cur) complexes. These complexes act as a molecular “Trojan horse” that hijacks bacterial iron‐acquisition pathways to induce ferroptosis. Concurrently, CHPB scavenges reactive oxygen species (ROS) via its intrinsic nanozyme activity and suppresses oxidative stress‐driven fibroblast activation, thereby dismantling the fibrotic barrier that excludes immune effector cells. This dual action eliminates biofilms and restores immune cell infiltration into the infection site. In preclinical animal models, the therapy clears established implant infections, remodels the immune‐fibrotic microenvironment, and promotes tissue regeneration. This work establishes a “clear‐and‐remodel” paradigm that integrates active targeted ferroptosis (via iron hijacking) with immuno‐fibrotic remodeling, offering a translatable strategy for complex implant‐associated biofilm infections.