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@CeO₂). This design leverages the intrinsic DNA-hydrolyzing activity of the CeO₂ 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@CeO₂ nanocomposite. Upon near-infrared light irradiation, the infiltrated nanocomposite generates localized hyperthermia, efficiently ablating deeply seated bacteria while simultaneously enhancing the catalytic activity of CeO₂. In vitro assays demonstrated superior biofilm penetration and disruption by the MN/OMCN@CeO₂ 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.