BACKGROUND Infectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest. RESULTS In this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo. CONCLUSIONS Our study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.

中文翻译：

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具有单NIR激光触发的光热和NO释放功能的多功能平台，用于针对多重耐药的革兰氏阴性细菌及其生物膜的协同治疗。

背景技术由多药耐药性（MDR）细菌，尤其是MDR革兰氏阴性菌株引起的传染病已经成为全球公共卫生挑战。通过消灭浮游细菌及其生物膜来控制MDR细菌感染的多功能纳米材料备受关注。结果在这项研究中，我们开发了具有单NIR激光触发的PTT和NO释放的多功能平台（TG-NO-B），以协同治疗MDR革兰氏阴性细菌及其生物膜。当位于感染部位时，TG-NO-B能够通过TG-NO-B的BA基团与细菌LPS单元之间的共价偶联，选择性地与革兰氏阴性细菌细胞及其生物膜基质结合。可以大大提高抗菌效率，并减少对周围正常组织的侧面伤害。在单次NIR激光照射下，TG-NO-B会产生高温并同时释放NO，这会协同破坏细菌细胞膜，进一步引起细胞内成分的泄漏和损坏，最终导致细菌死亡。一方面，NO和PTT的结合可以大大提高抗菌效果。另一方面，细菌细胞膜的损伤可提高通透性和对热的敏感性，降低光热温度并避免高温造成的损伤。此外，TG-NO-B可以有效地用于协同治疗MDR革兰氏阴性菌及其生物膜的体内感染，并加速伤口愈合，并在体外和体内均表现出优异的生物相容性。