A Biofilm‐Disrupting Microneedle Patch Leveraging DNA‐Hydrolyzing Nanozyme and Photothermia for Enhanced Diabetic Ulcer Therapy

ABSTRACT Biofilm‐infected diabetic ulcer represents a formidable clinical challenge due to the limited penetration and poor efficacy of conventional antimicrobials. Although photothermal therapy offers a non‐invasive alternative, its efficacy is severely constrained by the inadequate infiltration of photothermal agents into deep biofilm regions. To address this barrier, we engineered a dissolvable microneedle patch incorporating ceria‐decorated oxidized mesoporous carbon nanospheres (MN/OMCN@CeO 2 ). This design leverages the intrinsic DNA‐hydrolyzing activity of the CeO 2 nanozyme to selectively degrade extracellular DNA (eDNA), a key structural component of the biofilm matrix. Enzymatic disruption of eDNA loosens the biofilm structure, thereby facilitating the deep penetration of the OMCN@CeO 2 nanocomposite. Upon near‐infrared light irradiation, the infiltrated nanocomposite generates localized hyperthermia, efficiently ablating deeply seated bacteria while simultaneously enhancing the catalytic activity of CeO 2 . In vitro assays demonstrated superior biofilm penetration and disruption by the MN/OMCN@CeO 2 patch, along with robust bactericidal activity against Staphylococcus aureus and Escherichia coli . Further, in a murine model of diabetic ulcer biofilm infection, patch application significantly accelerated wound healing through effective bacterial clearance, attenuation of inflammatory responses, and promotion of tissue repair. Collectively, this DNA‐hydrolyzing nanozyme‐potentiated photothermal platform offers a promising therapeutic strategy for refractory, biofilm‐associated diabetic ulcers.