A Mucous Permeable Local Delivery Strategy Based on Manganese-Enhanced Bacterial Cuproptosis-like Death for Bacterial Pneumonia Treatment.

IF 15.8 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY ACS Nano Pub Date : 2024-11-07 DOI:10.1021/acsnano.4c09695
Shiyuan Hua, Huiqun Hu, Jin Liu, Feng Lu, Runchang Yu, Xuening Zhang, Haimeng Sun, Ziwei Wang, Yige Li, Jingyan Xia, Feng Xu, Min Zhou
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Abstract

Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects. Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in the aerobic bacteria of the lungs. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, which can interact with copper and thus hinder the interaction of copper with proteins and assist in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large number of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions are further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug-delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid systemic toxicity that can be caused by large doses of copper.

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基于锰强化细菌杯突样变死亡的粘膜渗透性局部给药策略,用于治疗细菌性肺炎。
细菌性肺炎是全球最具挑战性的传染病之一,发病率和死亡率都很高。考虑到抗生素的滥用和细菌生物膜的耐药性,人们开发了多种金属基材料。然而,由于肺部的高氧环境,一些需氧感染细菌对氧气和 ROS 有很高的耐受性,大多数基于 ROS 的金属基材料可能无法达到很好的治疗效果。受杯突症对需氧呼吸细胞敏感性的启发,我们设计了一种铜复合抗菌纳米粒子,并发现它能有效诱导肺部需氧细菌发生类似杯突症的死亡。为了解决杯突在体内应用的难题,我们首先加入了二氧化锰,以消耗保护性谷胱甘肽,谷胱甘肽可与铜相互作用,从而阻碍铜与蛋白质的相互作用,并通过免疫增强来协助抗菌作用。类铜中毒死亡还需要大量的铜离子。针对这一需求,我们通过局部给药的方式,递送正亲水性改性复合纳米颗粒,有效穿透肺粘液层直达肺部,铜离子在感染部位的酸性环境中进一步快速释放,与锰协同作用可进一步破坏细菌生物膜。这种给药系统可有效治疗需氧菌引起的肺炎,并避免大剂量铜可能引起的全身毒性。
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来源期刊
ACS Nano
ACS Nano 工程技术-材料科学:综合
CiteScore
26.00
自引率
4.10%
发文量
1627
审稿时长
1.7 months
期刊介绍: ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.
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