Chuang Zhang, Xiaolei Liu, Zipei Zhang, Zhili Hao, Xu Geng, Ning Jiang, Mingyuan Liu, Zhengqiang Li, Chen Li
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引用次数: 0
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.
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.