Charge Regulation-Enhanced Type I Photosensitizer-Loaded Hydrogel Dressing for Hypoxic Bacterial Inhibition and Biofilm Elimination

Biofilm-induced chronic bacterial infections represent a significant challenge in modern medicine due to their resistance to conventional antibiotic treatments. Although photodynamic therapy (PDT) has emerged as a promising antibiotic-free antibacterial strategy, the hypoxic condition within biofilms and the lack of an effective local drug delivery system have limited the clinical effectiveness of photosensitizer (PS) agents. Herein, we propose a type of charge regulation-enhanced type I PS-loaded hydrogel dressing for treating biofilm infection. The charge regulation enables the multiple alkylation Nile blue (EB series) to exhibit substantially improved absorbance (∼2-fold), alkaline tolerance, and superoxide anion yield (2.2–4.2-fold) compared to the representative type I PS, sulfur-substituted Nile blue. Specifically, the enhanced electronic push–pull capabilities promote a more efficient electron recycling process, significantly boosting the efficiency of type I PDT. The superior PDT effect and enhanced bacterial uptake via charge regulation render the EB series more pronounced in hypoxic bacterial inhibition under red light or sunlight irradiation. Moreover, the hydrogel, constructed from oxidized dextran and quaternized chitosan, facilitates the localization and sustained retention of type I PSs, accelerating the healing of biofilm-infected wounds. This type I PS-based hydrogel could provide an efficient and user-friendly wound dressing for the clinical treatment and prevention of biofilm infections.