Photothermal Nanozyme‐Based Microneedle Patch against Refractory Bacterial Biofilm Infection via Iron‐Actuated Janus Ion Therapy

Owing to high antibiotic resistance and thermotolerance, bacterial biofilm infections (BBIs) are refractory to elimination. Iron is essential for bacterial growth and metabolism, and bacteria can thus accumulate iron from surrounding cells to maintain biofilm formation and survival. Consequently, iron deficiency in the biofilm microenvironment (BME) leads to the functional failure of innate immune cells. Herein, a novel antibiofilm strategy of iron‐actuated Janus ion therapy (IJIT) is proposed to regulate iron metabolism in both bacterial biofilm and immune cells. A BME‐responsive photothermal microneedle patch (FGO@MN) is synthesized by the growth of Fe3O4 nanoparticles on graphene oxide nanosheets and then encapsulated in methacrylated hyaluronic acid needle tips. The catalytic product of ·OH by FGO@MN in BME disrupts the bacterial heat‐shock proteins, coercing biofilm thermal sensitization. As synergistic mild photothermal treatment triggers iron uptake, the intracellular iron overload further induces ferroptosis‐like death. Moreover, iron‐nourished neutrophils around BME can be rejuvenated for reactivating the suppressed antibiofilm function. Thus, more than 95% BBIs elimination can be achieved by combining heat stress‐triggered iron interference with iron‐nutrient immune reactivation. Furthermore, in vivo experiments validate the scavenging of refractory BBI after 15 days, suggesting the promising perspective of IJIT in future clinical application. A photothermal nanozyme‐based microneedle patch FGO@MN is fabricated for eliminating refractory bacterial biofilm infections. FGO@MN disrupts the bacterial biofilm heat‐shock response and induces ferroptosis‐like death in bacterial biofilm. Simultaneously, the suppressed neutrophils in biofilm microenvironment acquire iron nutrition to reactivate antibiofilm immune response. This dual‐modulation of iron metabolism by FGO@MN is referred to as a novel iron‐actuated Janus ion therapy.