A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms
A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms
复制标题
具有单近红外激光触发光热和一氧化氮释放的多功能平台，用于针对多重耐药革兰氏阴性菌及其生物膜的协同治疗
DOI：
10.1186/s12951-020-00614-5
复制
发表时间：
2020-04-15
影响因子：
10.2
通讯作者：
Qian, Wei
中科院分区：
文献类型：
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作者：
Zhao, Baohua;Wang, He;Qian, Wei
背景由耐多药（MDR）细菌，特别是革兰氏阴性菌株引起的传染病，已成为全球性的公共卫生挑战。通过清除浮游细菌及其生物膜来控制耐多药细菌感染的多功能纳米材料引起了人们的极大兴趣。结果在本研究中，我们建立了一个具有单次近红外激光触发PTT和NO释放的多功能平台（TG-NO-B），用于协同治疗MDR革兰氏阴性菌及其生物膜。当TG-NO-B位于感染部位时，通过TG-NO-B的BA基团与细菌LPS单元之间的共价偶联，可以选择性地结合到革兰氏阴性细菌细胞及其生物膜基质表面，从而大大提高了抗菌效率，减少了对周围正常组织的副作用。在单次近红外激光照射下，TG-NO-B可产生高温，同时释放NO，协同破坏细菌细胞膜，进一步造成细胞内组分的渗漏和损伤，最终诱导细菌死亡。一方面，NO与PTT联合使用可显著提高抗菌效率。另一方面，细菌细胞膜损伤可以提高细胞膜的通透性和对热的敏感性，降低光热温度，避免高温对细胞膜的损害。此外，TG-NO-B可以有效地协同治疗耐多药革兰氏阴性菌及其生物膜的体内感染，加速伤口愈合，并在体外和体内均具有良好的生物相容性。结论TG-NO-B是治疗耐多药革兰氏阴性菌及其生物膜感染的一种有前景的替代药物。
BackgroundInfectious 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.ResultsIn 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.ConclusionsOur 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.