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Bacterial infections in wounded skin are associated with high mortality. The emergence of drug-resistant bacteria in wounded skin has been a challenge. Toluidine blue (TB) is a safe and inexpensive photosensitizer that can be activated and used in near-infrared photodynamic therapy to effectively kill methicillin-resistant Staphylococcus aureus (MRSA). However, its aggregation-induced quenching effect largely affects its clinical applications. In this study, TB nanoparticles (NPs) were synthesized using an ultrasound-assisted coating method. Their physicochemical and biological properties were studied and evaluated by scanning electron microscopy and Fourier-transform infrared spectroscopy. The TBNPs had a broad-spectrum antibacterial activity against Gram-positive bacteria (MRSA) and Gram-negative bacteria (E. coli). In addition, MTT, hemolysis, and acute toxicity tests confirmed that TBNPs had good biocompatibility. The TBNPs exhibited a high photodynamic performance under laser irradiation and efficiently killed E. coli and MRSA through generated reactive oxygen species, which destroyed the cell wall structure. The potential application of TBNPs in vivo was studied using an MRSA-infected wound model. The TBNPs could promote wound healing within 7 days, mainly by reducing the inflammation and promoting collagen deposition and granulation tissue formation. In conclusion, the TBNPs offer a promising strategy for clinical applications against multiple-drug resistance.

Poly Lactic-co-Glycolic Acid-Coated Toluidine Blue Nanoparticles for the Antibacterial Therapy of Wounds