Wake biofilm up to enhance suicidal uptake of gallium for chronic lung infection treatment

IF 12.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Jian He , Xiuhui Lin , Dongxiao Zhang , Huiqun Hu , Xiaoyuan Chen , Feng Xu , Min Zhou
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Abstract

The hypometabolic and nutrient-limiting condition of dormant bacteria inside biofilms reduces their susceptibility to antibacterial agents, making the treatment of biofilm-dominating chronic infections difficult. Herein, we demonstrate an intratracheal aerosolized maltohexaose-modified catalase-gallium integrated nanosystem that can ‘wake up’ dormant Pseudomonas aeruginosa biofilm to increase the metabolism and nutritional iron demand by reconciling the oxygen gradient. The activated bacteria then enhance suicidal gallium uptake since gallium acts as a 'Trojan horse' to mimic iron. The internalized gallium ions disrupt biofilms by interfering with the physiological processes of iron ion acquisition and utilization, biofilm formation, and quorum sensing. Furthermore, aerosol microsprayer administration and bacteria-specific maltohexaose modification enable accumulation at biofilm-infected lung and targeted release of gallium into bacteria to improve the therapeutic effect. This work provides a potential strategy for treating infection by reversing the dormant biofilm's resistance condition.

唤醒生物膜以增强镓的自杀性吸收,从而治疗慢性肺部感染
生物膜内的休眠细菌处于低代谢和营养限制状态,这降低了它们对抗菌药物的敏感性,使得以生物膜为主的慢性感染难以治疗。在此,我们展示了一种气管内气溶胶化的麦芽己糖修饰过氧化氢酶-镓集成纳米系统,它能 "唤醒 "休眠的铜绿假单胞菌生物膜,通过调节氧梯度来增加新陈代谢和营养铁需求。由于镓是模拟铁的 "特洛伊木马",被激活的细菌会增强对镓的自杀性吸收。内化的镓离子会干扰铁离子的获取和利用、生物膜的形成以及法定量感应等生理过程,从而破坏生物膜。此外,气溶胶微喷雾器给药和细菌特异性麦芽六糖修饰可使镓在受生物膜感染的肺部积聚并定向释放到细菌中,从而提高治疗效果。这项研究为通过逆转休眠生物膜的抗药性条件来治疗感染提供了一种潜在的策略。
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来源期刊
Biomaterials
Biomaterials 工程技术-材料科学:生物材料
CiteScore
26.00
自引率
2.90%
发文量
565
审稿时长
46 days
期刊介绍: Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.
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