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用于高效治疗多重耐药细菌感染的PBA功能化单原子铁

PBA functionalized single-atom Fe for efficient therapy of multidrug-resistant bacterial infections.

作者信息

Yang Ruigeng, Wei Yueru, Zhao Mengyang, Shi Mengxiao, Zhao Yongxing, Sun Pengchao

机构信息

Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.

Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, Henan, PR China; Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, PR China.

出版信息

Colloids Surf B Biointerfaces. 2022 Nov;219:112811. doi: 10.1016/j.colsurfb.2022.112811. Epub 2022 Aug 28.

Abstract

The abuse of antibiotics has led to the emergence of multidrug-resistant bacterial strains worldwide, which greatly threatens human health. In the present work, we developed single-atom catalysts (SACs) with atomically dispersed Fe as catalytic sites (Fe-SACs) to combat multidrug-resistant bacteria by elevating cellular reactive oxygen species (ROS). Our intensive studies confirmed that Fe-SACs were successfully prepared and exhibited excellent catalase (CAT)-, oxidase (OXD)-, and peroxidase (POD)-like activities. To enhance water dispersibility, biosafety and the interactions between the nanodrugs and gram-positive bacteria, phenylboronic acid group-functionalized carboxylated chitosan (CCS-PBA) was coated on the surface of Fe-SACs to yield Fe-SACs@CCS-PBA for in vitro and in vivo studies. The synergistic catalytic activity and photothermal activity of Fe-SACs@CCS-PBA effectively overcame multidrug-resistant bacterial strains (MRSA) in vitro and significantly accelerated wound healing in vivo, suggesting the great potential of SACs to overcome infectious disease caused by multidrug-resistant bacteria.

摘要

抗生素的滥用已导致全球范围内多重耐药细菌菌株的出现,这对人类健康构成了巨大威胁。在本研究中,我们开发了以原子分散的铁作为催化位点的单原子催化剂(SACs)(Fe-SACs),通过提高细胞活性氧(ROS)来对抗多重耐药细菌。我们的深入研究证实,成功制备了Fe-SACs,其表现出优异的过氧化氢酶(CAT)、氧化酶(OXD)和过氧化物酶(POD)样活性。为了提高水分散性、生物安全性以及纳米药物与革兰氏阳性菌之间的相互作用,在Fe-SACs表面包覆了苯基硼酸基团功能化的羧甲基壳聚糖(CCS-PBA),以制备用于体外和体内研究的Fe-SACs@CCS-PBA。Fe-SACs@CCS-PBA的协同催化活性和光热活性在体外有效克服了多重耐药细菌菌株(MRSA),并在体内显著加速了伤口愈合,这表明SACs在克服多重耐药细菌引起的传染病方面具有巨大潜力。

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