A Natural Enzyme GOx-MOF Cascade Complex Killing Zoonotic Parasite Trichinella spiralis by Energy Utilization Limitation and Generated Free Radicals

IF 2.6 2区 农林科学 Q2 INFECTIOUS DISEASES
Chuang Zhang, Xiaolei Liu, Zipei Zhang, Zhili Hao, Xu Geng, Ning Jiang, Mingyuan Liu, Zhengqiang Li, Chen Li
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Abstract

Nanozymes offer promising alternatives to natural enzymes due to enhanced stability, tunable activity, and cost efficiency, demonstrating therapeutic potential against tumors, infections, and inflammatory disorders. Trichinella spiralis is an important pathogen, which globally prevalent foodborne zoonotic parasite. Chemical drug is commonly used to kill T. spiralis, but there are risks of chemical abuse and drug resistance. Here, we engineered MPG(Fe), a cascade nanozyme formed by covalently conjugating glucose oxidase (GOx) to a metal-organic framework-Fe nanozyme (MOF-525[Fe]) nanozyme via the bifunctional PEG linker. In vitro, MPG(Fe) depleted glucose through GOx-catalyzed conversion to gluconic acid and H2O2, while MOF-525(Fe) subsequently transformed H2O2 into cytotoxic hydroxyl radicals (•OH). This dual-action mechanism dose-dependently killed intestinal-stage adult worms and newborn larvae (NBL) of T. spiralis. In a BALB/c mouse model of intestinal T. spiralis infection, high-dose MPG(Fe) reduced the survival of intestinal adult worms to 3.53% of the control value through the synergistic actions of glucose deprivation and hydroxyl radical (•OH)-mediated oxidative damage. Critically, MPG(Fe) exhibited no tissue toxicity in uninfected mice. Our findings establish enzyme-mimetic nanozymes as a novel therapeutic platform against zoonotic helminthiases.

天然酶GOx-MOF级联复合物通过能量利用限制和产生自由基杀死人畜共患寄生虫旋毛虫。
纳米酶具有更高的稳定性、可调节的活性和成本效益,为天然酶提供了有希望的替代品,显示出治疗肿瘤、感染和炎症性疾病的潜力。旋毛虫是一种重要的致病菌,是全球流行的食源性人畜共患寄生虫。化学药物通常用于杀死螺旋体,但存在化学药物滥用和耐药性的风险。在这里,我们设计了MPG(Fe),这是一种级联纳米酶,通过双功能PEG连接物将葡萄糖氧化酶(GOx)共价偶联到金属-有机框架-铁纳米酶(MOF-525[Fe])纳米酶上。在体外,MPG(Fe)通过gox催化将葡萄糖转化为葡萄糖酸和H2O2来消耗葡萄糖,而MOF-525(Fe)随后将H2O2转化为细胞毒性羟基自由基(•OH)。这种双重作用机制剂量依赖性地杀死了螺旋体绦虫肠期成虫和新生幼虫。在肠螺旋体感染BALB/c小鼠模型中,高剂量MPG(Fe)通过葡萄糖剥夺和羟基自由基(•OH)介导的氧化损伤的协同作用,使肠成虫的存活率降低到控制值的3.53%。关键的是,MPG(Fe)在未感染的小鼠中没有表现出组织毒性。我们的研究结果建立了模拟酶纳米酶作为对抗人畜共患蠕虫病的新治疗平台。
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来源期刊
Transboundary and Emerging Diseases
Transboundary and Emerging Diseases 农林科学-传染病学
CiteScore
8.90
自引率
9.30%
发文量
350
审稿时长
1 months
期刊介绍: Transboundary and Emerging Diseases brings together in one place the latest research on infectious diseases considered to hold the greatest economic threat to animals and humans worldwide. The journal provides a venue for global research on their diagnosis, prevention and management, and for papers on public health, pathogenesis, epidemiology, statistical modeling, diagnostics, biosecurity issues, genomics, vaccine development and rapid communication of new outbreaks. Papers should include timely research approaches using state-of-the-art technologies. The editors encourage papers adopting a science-based approach on socio-economic and environmental factors influencing the management of the bio-security threat posed by these diseases, including risk analysis and disease spread modeling. Preference will be given to communications focusing on novel science-based approaches to controlling transboundary and emerging diseases. The following topics are generally considered out-of-scope, but decisions are made on a case-by-case basis (for example, studies on cryptic wildlife populations, and those on potential species extinctions): Pathogen discovery: a common pathogen newly recognised in a specific country, or a new pathogen or genetic sequence for which there is little context about — or insights regarding — its emergence or spread. Prevalence estimation surveys and risk factor studies based on survey (rather than longitudinal) methodology, except when such studies are unique. Surveys of knowledge, attitudes and practices are within scope. Diagnostic test development if not accompanied by robust sensitivity and specificity estimation from field studies. Studies focused only on laboratory methods in which relevance to disease emergence and spread is not obvious or can not be inferred (“pure research” type studies). Narrative literature reviews which do not generate new knowledge. Systematic and scoping reviews, and meta-analyses are within scope.
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