Phenylboronic acid-modified carbon dot-proteinase K nanohybrids for enhanced photodynamic therapy against bacterial biofilm infections.

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Nanohybrids combining phenylboronic acid-modified carbon dots (PCDs) and proteinase K have been engineered for addressing the formidable challenges of antimicrobial photodynamic therapy (aPDT) against bacterial biofilm infections, overcoming biofilm barrier obstruction, the limited diffusion of reactive oxygen species (ROS), and the inadequate ROS generation of traditional photosensitizers. PCDs are formulated for superior water solubility and robust singlet oxygen (1O2) production, mitigating issues related to dispersion and aggregation-induced quenching typical of conventional photosensitizers. The conjugation of phenylboronic acid to CDs not only enhanced 1O2 generation through increased electron-hole separation but also imparted strong bacterial binding capabilities to the PCDs, enabling broad-spectrum sterilization by maximizing the ROS-mediated bacterial destruction. Proteinase K, serving as a structural "glue", actively breaks down biofilms and facilitates the deep penetration of functional PCDs, aiding effective treatment of biofilm infections. In vivo studies confirm that PCDs-proteinase K nanohybrids dramatically accelerate healing in biofilm-infected wounds by synergizing enhanced photosensitization, potent bacterial adherence, and efficient biofilm elimination and penetration. This approach highlights a straightforward strategy to significantly advance aPDT, promoting the clinical adoption of non-antibiotic methods for combating bacterial biofilm infections. STATEMENT OF SIGNIFICANCE: 1) Phenylboronic acid-modified carbon dots (PCDs) were designed for enhanced water solubility and efficient singlet oxygen generation through surface modulation, also suggesting that surface modification can improve the inherent photosensitizing activity of CDs by promoting electron-hole separation; 2) The conjugation of phenylboronic acid endowed PCDs with strong bacterial binding capabilities, enabling highly efficient and broad-spectrum sterilization by maximizing reactive oxygen species-mediated bacterial destruction; 3) Incorporation of proteinase K (PK) leveraged its specific extracellular polymeric substance degrading capability, along with the stimuli-responsive release of PCDs from the PCDs-PK nanohybrids, facilitating biofilm breakdown and enabling deeper penetration of PCDs, thereby improving the treatment of biofilm infections.