Treating Multi-Drug-Resistant Bacterial Infections by Functionalized Nano-Bismuth Sulfide through the Synergy of Immunotherapy and Bacteria-Sensitive Phototherapy.

Abstract

Owing to its flexibility and high treatment efficiency, phototherapy is rapidly emerging for treating bacteria-induced diseases, but how to improve the sensitivity of bacteria to reactive oxygen species (ROS) and heat simultaneously to kill bacteria under mild conditions is still a challenge. Herein, we designed a NIR light catalyst (Bi₂S₃-<i>S</i>-nitrosothiol-acetylcholine (BSNA)) by transforming ^•O₂^- into peroxynitrite <i>in situ</i>, which can enhance the bacterial sensibility to ROS and heat and kill bacteria under a mild temperature. The transformed peroxynitrite <i>in situ</i> possessed a stronger ability to penetrate cell membranes and antioxidant capacity. The BSNA nanoparticles (NPs) inhibited the bacterial glucose metabolic process through down-regulated xerC/xerD expression and disrupted the HSP70/HSP90 secondary structure through nitrifying TYR179. Additionally, the synergistic effect of the designed BSNA and clinical antibiotics increased the antibacterial activity. In the case of tetracycline-class antibiotics, BSNA NPs induced phenolic hydroxyl group structure changes and inhibited the interaction between tetracycline and targeted t-RNA recombinant protein. Besides, BSNA stimulated production of more CD8⁺ T cells and reduced common complications in peritonitis, which provided immunotherapy activity. The targeted and anti-infective effect of BSNA suggested that we propose a nanotherapeutic strategy to achieve more efficient synergistic therapy under mild temperatures.