Photothermally triggered nitric oxide nanogenerator targeting type IV pili for precise therapy of bacterial infections.

Nitric oxide (NO) is an important biological messenger involved in the treatment of bacterial infections, but its controlled and targeted release in bacterial infections remains a major challenge. Herein, an intelligent NO nanogenerator triggered by near-infrared (NIR) light is constructed for targeted treatment of P. aeruginosa bacterial infection. Since maleimide can recognize and attach to the pilus of T4P of P. aeruginosa, we adopt this strategy to achieve the accurate release of therapeutic drugs at the infection site, i.e., after maleimide targets Gram-negative bacteria, the SNP@MOF@Au-Mal nanogenerator will release NO and generate ROS in situ from the inorganic photosensitizer gold nanoparticles under NIR irradiation to achieve synergistic antibacterial effect. In vivo experiments proved that the bacterial burden on the wound was reduced by 97.7%. Additionally, the nanogenerator was shown to promote the secretion of growth factors, which play a key role in regulating inflammation and inducing angiogenesis. This strategy has the advantage of generating a high concentration of NO in situ to promote the transfer of more NO and its derivatives (N2O3, ONOO-) to bacteria, thereby significantly improving the antibacterial effect. The multifunctional antibacterial platform has been demonstrated as a good carrier for gas therapy because of its simple and efficient gas release performance, indicating its great potential for the treatment of drug-resistant bacterial infections.