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-S-nitrosothiol-acetylcholine (BSNA)) by transforming •O2- into peroxynitrite in situ, which can enhance the bacterial sensibility to ROS and heat and kill bacteria under a mild temperature. The transformed peroxynitrite in situ 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.
Authors	Yuan Li, Xiangmei Liu, Zhenduo Cui, Yufeng Zheng, Hui Jiang, Yu Zhang, Yanqin Liang, Zhaoyang Li, Shengli Zhu, Shuilin Wu
Journal	ACS nano (ACS Nano) Vol. 16 Issue 9 Pg. 14860-14873 (09 27 2022) ISSN: 1936-086X [Electronic] United States
PMID	36094899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Anti-Bacterial Agents Antioxidants Reactive Oxygen Species Recombinant Proteins S-Nitrosothiols Sulfides Tetracyclines Peroxynitrous Acid RNA Glucose Acetylcholine Bismuth bismuth sulfide
Topics	Acetylcholine Anti-Bacterial Agents (chemistry, pharmacology, therapeutic use) Antioxidants Bacteria (metabolism) Bacterial Infections (drug therapy) Bismuth CD8-Positive T-Lymphocytes Glucose Humans Immunotherapy Nanoparticles (chemistry) Peroxynitrous Acid Phototherapy RNA Reactive Oxygen Species (metabolism) Recombinant Proteins S-Nitrosothiols Sulfides (chemistry, pharmacology, therapeutic use) Tetracyclines

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