Lipase-Activated MnO2 Nanoflowers for Precise Biofilm Imaging and Oxygen-Enhanced Sonodynamic Therapy to Promote Diabetic Wound Healing

Diabetic wound healing is substantially impaired by biofilm infections, oxidative stress, and persistent hypoxia, which present major challenges for timely diagnosis and treatment. In this study, theranostic nanoparticles (NPs) were engineered to facilitate lipase-triggered biofilm theranostics and accelerate wound healing. Theranostic Mn-TC NPs were prepared by grafting a fluorescent sonosensitizer, meso-tetra (4-carboxyphenyl) porphine (TCPP), onto manganese dioxide (MnO 2 ) nanoflowers, quenching the fluorescence emissions of TCPP. Upon encountering biofilms in vivo, the elevated lipase hydrolyzes ester linkages within the Mn-TC NPs, liberating TCPP to restore its fluorescence emission and enabling the real-time visualization of biofilm-infected wounds. MnO 2 nanoflowers offer abundant reaction sites for TCPP grafting while enhancing the catalysis of hydrogen peroxide to generate oxygen. The boosted oxygen evolution promoted the sonodynamic therapy effect of ultrasound-activated TCPP, achieving 94.0% reduction in biofilm biomass and 99.9% bacterial clearance. Engineering NPs accelerate wound healing by simultaneously eradicating biofilms, modulating inflammatory states, enhancing collagen deposition, and promoting angiogenesis. This study presents a novel theranostic strategy for biofilm-triggered visual imaging and an antibiotic-free therapy for diabetic wounds.