BODIPY-based nanoparticles for highly efficient photothermal/gas synergistic therapy against drug-resistant bacterial infection

Drug-resistant bacterial wound infections have become a major threat to human health worldwide, and there is an urgent need to develop a new generation of antibacterial agents to replace conventional antibiotics. In this work, we proposed an efficient nanoplatform that combines photothermal therapy (PTT) and light-triggered release of nitric oxide (NO) to combat bacteria. A multifunctional nanoplatform (BBDH NPs) based on a BODIPY probe, NO thermal responsive donor [N, N′-di-sec-butyl-N, N′-diniroso-1,4-phenylenediamine (BNN6)], and a PEGylated polymer was prepared with a nanoprecipitation method. BBDH NPs represent a one-two punch against bacterial infections, combining potent photothermal therapy and the controlled release of NO, enabling rapid and efficient eradication of gram-negative and gram-positive bacteria. Histological analysis on a mouse model demonstrates that wounds treated with BBDH NPs and 685 nm laser irradiation have completed re-epithelialization, significant collagen deposition, and a number of hair follicle formation. BBDH NPs also exhibit a remarkable therapeutic effect on wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). These results highlight that the proposed synergistic antibacterial strategy can be used as a potential therapeutic tool in drug-resistant, bacterial-infected wounds. Graphical Abstract: (Figure presented.)