A dual-targeted platform based on graphene for synergistic chemo-photothermal therapy against multidrug-resistant Gram-negative bacteria and their biofilms

A dual-targeted platform based on graphene for synergistic chemo-photothermal therapy against multidrug-resistant Gram-negative bacteria and their biofilms
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基于石墨烯的双靶点平台,用于协同化学光热疗法对抗多重耐药革兰氏阴性菌及其生物膜

DOI:
10.1016/j.cej.2020.124595
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发表时间:
2020-08
影响因子:
15.1
通讯作者:
Qian Wei
Qian Wei
中科院分区:
工程技术1区
文献类型:
--
作者:
Wang He;Zhao Baohua;Dong Wenjing;Zhong Yuan;Zhang Xiaorong;Gong Yali;Zhan Rixing;Xing Malcolm;Zhang Jianxiang;Luo Gaoxing;Qian Wei

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多模式靶向治疗平台的构建是对抗多药耐药(MDR)细菌相关感染的一种有前途的策略。我们报道了一种基于硼酸功能化的石墨烯基季铵盐(B-CG-QAS)的双靶向抗菌平台,其整合了协同的化学-光热效应。当定位于革兰氏阴性菌相关感染部位时,B-CG-QAS能够通过静电粘附(QAS)和共价偶联(BA)的双重作用与细菌及其生物膜特异性结合,从而导致比单靶向药物(B-CG或CG-QAS)更上级的靶向能力,提高杀菌效力,减少QAS的剂量并且最小化化疗/光热毒性。除了QAS介导的抗菌作用外,近红外激光照射CG可通过协同热疗进一步提高抗菌效果。另一方面,QAS可以破坏细菌细胞膜,提高其通透性和对热的敏感性。此外,B-CG-QAS可有效地用于协同化学光热治疗MDR革兰阴性菌及其生物膜的体内感染,促进细菌感染伤口的愈合,并在体内外均表现出良好的生物相容性。因此,我们的研究表明B-CG-QAS具有治疗MDR革兰阴性菌感染及其生物膜的巨大潜力。
The construction of multimodal targeting and therapeutic platforms is a promising strategy for combating multidrug-resistant (MDR) bacteria-associated infections. We report a dual-targeted antibacterial platform integrating a synergistic chemo-photothermal effect based on the boronic acid functionalized graphene-based quaternary ammonium salt (B-CG-QAS). When located at the sites of Gram-negative bacteria associated infections, B-CG-QAS was able to specifically bind to the bacteria and their biofilms via the dual effect of electrostatic adhesion (QAS) and covalent coupling (BA), resulting in a superior targeting ability over the single-targeted agents (B-CG or CG-QAS), improved bactericidal efficacy, a reduced dose of QAS and minimized chemotherapeutic/photothermal toxicity. In addition to the QAS-mediated antibacterial effects, NIR laser irradiation onto CG could further improve the antimicrobial effect via the synergy of hyperthermia. On the other hand, QAS could disrupt the bacterial cell membrane and improve its permeability and sensitivity to heat. Moreover, B-CG-QAS could be effectively utilized for synergistic chemo-photothermal therapy against thein vivoinfections of MDR Gram-negative bacteria and their biofilms and accelerate bacteria-infected wound healing as well as exhibit outstanding biocompatibility bothin vitroandin vivo. Therefore, our study demonstrates that B-CG-QAS has great potential to treat MDR Gram-negative bacterial infections and their biofilms.
局部应用第四纪铵化合物Docyldimethylamonium溴化物后,发散的超敏反应。
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