Photodynamic and photothermal co-driven CO-enhanced multi-mode synergistic antibacterial nanoplatform to effectively fight against biofilm infections

Photothermal therapy (PTT) and photodynamic therapy (PDT) have garnered much attention for effectively treating biofilm infections. However, even highly efficient PTT reagents and photosensitizers still require high concentration and irradiation doses to ablate biofilms due to their limited permeability in biofilms, while these attempts tend to cause severe tissue damage and inflammation. Herein, a CO-enhanced multi-mode synergistic antibacterial nanoplatform (ICG&CO@G3KBPY) with controllable CO generation behavior, notably enhanced biofilm penetration, antibacterial, biofilm ablation, and anti-inflammatory activity was effectively developed to combat biofilm infections. ICG&CO@G3KBPY is constructed by physically encapsulating indocyanine green (ICG) and manganese pentacarbonyl bromide (MnBr(CO)5) into a 2,2′-bipyridine-4-carboxylic (BPY)-modified peptide dendrimer-based nanogel (G3KBPY). ICG&CO@G3KBPY can rapidly generate massive quantities of CO under the co-driven effects of PTT and PDT. Notably, the generated CO not only promotes the biofilm penetration of ICG and enhances the antibacterial and biofilm eradication performance of PTT and PDT, but also significantly alleviates the inflammatory response caused by bacterial infection, PTT and PDT. The combination of CO, PTT, and PDT offers excellent biofilm ablation effects in treating urinary catheter infection and subcutaneous abscesses, accompanied by good biocompatibility. This study provides an efficient and safe multi-mode synergistic antibacterial strategy for combatting biofilm infections.