Multifunctional Silk Fibroin Nanocarriers Loaded with Chlorin e6 for PDT/PTT Synergistic Elimination of Drug-Resistant Bacteria and Biofilms.

The development of drug-resistant biofilms has resulted in treatment failures for multidrug resistant (MDR) bacteria, presenting a substantial challenge to global public health. Consequently, the development of antibacterial agents has become an urgent priority. To overcome the limitations of poor penetration and inadequate efficacy of single-modal treatments for MDR bacterial biofilm infections, this study developed a Ce6/SFP nanocomposite system utilizing silk fibroin and polydopamine. The nanoparticles, fabricated via a desolvation-in situ polymerization method, demonstrated pH-responsive drug release properties. When subjected to an 808 nm NIR laser, the material exhibited a photothermal conversion efficiency of 29.3%. Furthermore, when paired with singlet oxygen produced through 660 nm excitation, it was highly effective in eliminating MDR Escherichia coli and MDR Staphylococcus aureus. The synergistic effect of photothermal therapy (PTT) and photodynamic therapy (PDT) disrupted the stability of the cell membrane and enhanced the antibacterial efficacy. Experimental results showed that the photothermal effect increased biofilm permeability, significantly improving Ce6 penetration depth. Moreover, in vivo treatments exhibited accelerated wound healing. Biocompatibility assessments revealed a hemolysis rate below 5% and no pathological damage to major organs. This study proposes a synergistic strategy to effectively address the challenges posed by biofilms and bacterial resistance.