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体内激活 pH 响应氧化酶样石墨纳米酶用于选择性杀灭幽门螺杆菌。

In vivo activation of pH-responsive oxidase-like graphitic nanozymes for selective killing of Helicobacter pylori.

机构信息

Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha, China.

Department of Gastroenterology, the Third Xiangya Hospital of Central South University, Changsha, China.

出版信息

Nat Commun. 2021 Mar 31;12(1):2002. doi: 10.1038/s41467-021-22286-x.

Abstract

Helicobacter pylori infection is a major etiological factor in gastric diseases. However, clinical antibiotic therapy for H. pylori is limited by continuously decreased therapeutic efficacy and side effects to symbiotic bacteria. Herein, we develop an in vivo activatable pH-responsive graphitic nanozyme, PtCo@Graphene (PtCo@G), for selective treatment of H. pylori. Such nanozymes can resist gastric acid corrosion, exhibit oxidase-like activity to stably generate reactive oxygen species only in acidic gastric milieu and demonstrate superior selective bactericidal property. C-PEG-Benzeneboronic acid molecules are modified on PtCo@G, improving its targeting capability. Under acidic gastric pH, graphitic nanozymes show notable bactericidal activity toward H. pylori, while no bacterial killing is observed under intestinal conditions. In mouse model, high antibacterial capability toward H. pylori and negligible side effects toward normal tissues and symbiotic bacteria are achieved. Graphitic nanozyme displays the desired enzyme-like activities at corresponding physiological sites and may address critical issues in clinical treatment of H. pylori infections.

摘要

幽门螺杆菌感染是导致胃部疾病的主要病因之一。然而,临床抗生素治疗幽门螺杆菌的疗效不断下降,且对共生菌存在副作用。在此,我们开发了一种体内可激活的 pH 响应石墨纳米酶,PtCo@Graphene(PtCo@G),用于选择性治疗幽门螺杆菌。这种纳米酶可以抵抗胃酸腐蚀,在酸性胃环境中表现出类似氧化酶的活性,仅能稳定地产生活性氧,并具有优异的选择性杀菌性能。PtCo@G 上修饰了 C-PEG-苯硼酸分子,提高了其靶向能力。在酸性胃液 pH 值下,石墨纳米酶对幽门螺杆菌具有显著的杀菌活性,而在肠道条件下则观察不到细菌杀伤作用。在小鼠模型中,PtCo@G 对幽门螺杆菌具有高抗菌能力,对正常组织和共生菌几乎没有副作用。石墨纳米酶在相应的生理部位显示出所需的酶样活性,可能解决幽门螺杆菌感染临床治疗中的关键问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d899/8012368/a7c2e58c510c/41467_2021_22286_Fig1_HTML.jpg

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