一种可光活化的苯基硼酸功能化纳米组件,用于对抗多重耐药革兰氏阴性菌及其生物膜。

IF 6.3 1区 医学 Q1 DERMATOLOGY Burns & Trauma Pub Date : 2023-10-16 eCollection Date: 2023-01-01 DOI:10.1093/burnst/tkad041
Xiaoqing Zhou, Lanlan Dong, Baohua Zhao, Guangyun Hu, Can Huang, Tengfei Liu, Yifei Lu, Mengxue Zheng, Yanlan Yu, Zengjun Yang, Shaowen Cheng, Yan Xiong, Gaoxing Luo, Wei Qian, Rui Yin
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引用次数: 0

摘要

背景:多重耐药(MDR)革兰氏阴性菌相关传染病已导致公共卫生负担和死亡率的增加。此外,生物膜的形成使这些细菌难以控制。因此,迫切需要开发新的干预措施来对抗耐多药革兰氏阴性菌及其生物膜相关感染。本研究的目的是开发一种基于IR-780和N,N'-二-叔丁基-N,N'--二硝基-1,4-苯二胺(BNN6)的多功能纳米组装体(IRNB),对革兰氏阴性菌引起的感染伤口和皮下脓肿具有协同作用。方法:研究IRNB的特性及其对细菌的靶向性。通过结晶紫染色法、平板计数法和体外活/死染色法证明了IRNB对革兰氏阴性菌及其生物膜的杀菌效果。在体内皮下脓肿和皮肤感染伤口模型上检测IRNB的抗菌效果。采用细胞计数试剂盒-8法、Calcein/PI细胞毒性法、溶血法和静脉注射法检测IRNB的体内外生物相容性。结果:在此,我们成功开发了一种基于IR-780和BNN6的多功能纳米组件IRNB,用于808nm激光触发的协同光热治疗(PTT)、光动力治疗(PDT)和一氧化氮(NO)效应。这种纳米组装体可以通过共价偶联效应在耐多药革兰氏阴性菌及其生物膜的感染部位特异性积累。在用808nm激光照射时,IRNB被激活并产生活性氧(ROS)和高温。局部高温可诱导NO生成,NO与ROS进一步反应生成ONOO-,从而增强杀菌效果。此外,NO和ONOO-可以破坏细胞膜,将细菌转化为极其敏感的状态,并进一步增强光热效应。在这项研究中,IRNB对革兰氏阴性菌引起的感染伤口和皮下脓肿显示出优越的光热光动力化学(NO)协同治疗效果。这导致了对相关感染的有效控制、炎症的缓解、再上皮化和胶原沉积的促进以及伤口愈合过程中血管生成的调节。此外,IRNB在体外和体内均表现出良好的生物相容性。结论:目前的研究表明,IRNB可以被认为是治疗耐多药革兰氏阴性菌及其生物膜引起的感染的一种有前途的替代方案。
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A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms.

Background: Multidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover, the formation of biofilms makes these bacteria difficult to control. Therefore, developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N, N'-di-sec-butyl-N, N'- dinitroso-1,4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.

Methods: The characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay, plate counting method and live/dead staining in vitro. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo. A cell counting kit-8 assay, Calcein/PI cytotoxicity assay, hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo.

Results: Herein, we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT), photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser, IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation, which further reacted with ROS to generate ONOO-, leading to the enhancement of bactericidal efficacy. Furthermore, NO and ONOO- could disrupt the cell membrane, which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study, IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections, relief of inflammation, promotion of re-epithelization and collagen deposition, and regulation of angiogenesis during wound healing. Moreover, IRNB exhibited excellent biocompatibility, both in vitro and in vivo.

Conclusions: The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.

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来源期刊
Burns & Trauma
Burns & Trauma 医学-皮肤病学
CiteScore
8.40
自引率
9.40%
发文量
186
审稿时长
6 weeks
期刊介绍: The first open access journal in the field of burns and trauma injury in the Asia-Pacific region, Burns & Trauma publishes the latest developments in basic, clinical and translational research in the field. With a special focus on prevention, clinical treatment and basic research, the journal welcomes submissions in various aspects of biomaterials, tissue engineering, stem cells, critical care, immunobiology, skin transplantation, and the prevention and regeneration of burns and trauma injuries. With an expert Editorial Board and a team of dedicated scientific editors, the journal enjoys a large readership and is supported by Southwest Hospital, which covers authors'' article processing charges.
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