Ultrasound-activated bimetallic PtRu alloy nanozymes for synergistic sonodynamic and chemodynamic therapy of multidrug-resistant bacterial infection

IF 10.2 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Xiang Zheng , Lingxia Pang , Youpei Wang , Qianlei Zhao , Guoquan Pan , Xiaojun He , Yafeng Liang
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引用次数: 0

Abstract

Deep-seated infections caused by multidrug-resistant (MDR) bacteria, such as pneumonia and abscesses, present significant therapeutic challenges due to their complex pathological microenvironments, which often limit the efficacy of conventional antibiotic treatments. The increasing emergence of MDR bacteria, along with their ability to rapidly acquire resistance, has intensified the need for novel therapeutic strategies. The advancement of nanotechnology has facilitated the development of non-antibiotic-dependent treatment modalities, which are increasingly preferred due to their high efficiency, non-invasiveness, and resistance-free properties. In this study, guided by density functional theory (DFT) predictions, we designed an ultrasound (US)-activated bimetallic PtxRuy alloy nanozyme (PR) that synergistically combines US-activated sonodynamic therapy (SDT) with chemodynamic therapy (CDT) for precise control of reactive oxygen species (ROS) generation. By carefully optimizing the atomic ratio of platinum (Pt, catalytic sites) to ruthenium (Ru, adsorption sites), we synthesized ultrafine bimetallic alloy nanoplatforms with enhanced functional performance. Both theoretical simulations and experimental characterizations confirmed that PR exhibits exceptional oxidase-like and peroxidase-like activity, facilitating enhanced US-triggered ROS production through amplified sonodynamic effects. The PR demonstrated significant in vitro antibacterial activity, effectively disrupted biofilms, and showed excellent biocompatibility. In mouse models of pneumonia and subcutaneous abscesses, PR facilitated rapid bacterial clearance and modulation of the inflammatory microenvironment. This study presents a novel, non-antibiotic biocatalytic platform that provides a rational design strategy for bimetallic alloy nanozymes, offering a promising therapeutic approach for the synergistic treatment of MDR bacterial infections. These findings underscore the translational potential of multifunctional nanoplatforms in addressing the growing challenge of antibiotic resistance.

Abstract Image

超声激活双金属PtRu合金纳米酶协同声动力和化学动力治疗多重耐药细菌感染
多药耐药(MDR)细菌引起的深层感染,如肺炎和脓肿,由于其复杂的病理微环境,往往限制了传统抗生素治疗的效果,因此给治疗带来了重大挑战。耐多药细菌的日益出现,以及它们迅速获得耐药性的能力,加强了对新的治疗策略的需求。纳米技术的进步促进了非抗生素依赖治疗方式的发展,由于其高效率、无侵入性和无耐药性的特性,这种治疗方式越来越受到人们的青睐。在本研究中,在密度泛函数理论(DFT)预测的指导下,我们设计了一种超声(US)激活的双金属PtxRuy合金纳米酶(PR),该纳米酶将US激活的声动力治疗(SDT)与化学动力治疗(CDT)协同结合,以精确控制活性氧(ROS)的产生。通过精心优化铂(Pt,催化位点)与钌(Ru,吸附位点)的原子比,我们合成了具有增强功能性能的超细双金属合金纳米平台。理论模拟和实验表征均证实,PR表现出异常的氧化酶样和过氧化物酶样活性,通过放大声动力效应促进us触发的ROS生成。PR具有显著的体外抗菌活性,能有效地破坏生物膜,并具有良好的生物相容性。在小鼠肺炎和皮下脓肿模型中,PR促进了细菌的快速清除和炎症微环境的调节。本研究提出了一种新的非抗生素生物催化平台,为双金属合金纳米酶的合理设计策略提供了一种有前途的治疗方法,用于协同治疗耐多药细菌感染。这些发现强调了多功能纳米平台在解决日益严峻的抗生素耐药性挑战方面的转化潜力。
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来源期刊
CiteScore
8.30
自引率
4.90%
发文量
303
审稿时长
30 days
期刊介绍: Materials Today Bio is a multidisciplinary journal that specializes in the intersection between biology and materials science, chemistry, physics, engineering, and medicine. It covers various aspects such as the design and assembly of new structures, their interaction with biological systems, functionalization, bioimaging, therapies, and diagnostics in healthcare. The journal aims to showcase the most significant advancements and discoveries in this field. As part of the Materials Today family, Materials Today Bio provides rigorous peer review, quick decision-making, and high visibility for authors. It is indexed in Scopus, PubMed Central, Emerging Sources, Citation Index (ESCI), and Directory of Open Access Journals (DOAJ).
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