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四面体型框架核酸:一种用于治疗抗生素耐药性感染的新策略。

Tetrahedral Framework Nucleic Acids: A Novel Strategy for Antibiotic Treating Drug-Resistant Infections.

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu, Sichuan 610041, China.

出版信息

Biomacromolecules. 2023 Feb 13;24(2):1052-1060. doi: 10.1021/acs.biomac.2c01525. Epub 2023 Feb 1.

DOI:10.1021/acs.biomac.2c01525
PMID:36723425
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10069167/
Abstract

Antibiotic multiresistance (AMR) has emerged as a major threat to human health as millions of people die from AMR-related problems every year. As has been witnessed during the global COVID-19 pandemic, the significantly increased demand for antibiotics has aggravated the issue of AMR. Therefore, there is an urgent need to find ways to alleviate it. Tetrahedral framework nucleic acids (tFNAs) are novel nanomaterials that are often used as drug delivery platforms because of their structural diversity. This study formed a tFNAs-antibiotic compound (TAC) which has a strong growth inhibitory effect on and methicillin-resistant () in vitro owing to the increased absorption of antibiotics by bacteria and improved drug movement across cell membranes. We established a mouse model of systemic peritonitis and local wound infections. The TAC exhibited good biosafety and improved the survival rate of severely infected mice, promoting the healing of local infections. In addition to the better transport of antibiotics to the target, the TAC may also enhance immunity by regulating the differentiation of M1 and M2 macrophages, providing a new option for the treatment of infections.

摘要

抗生素耐药性 (AMR) 已成为人类健康的主要威胁,每年有数百万人死于与 AMR 相关的问题。正如在全球 COVID-19 大流行期间所见证的那样,对抗生素的需求大幅增加加剧了 AMR 问题。因此,迫切需要寻找缓解这一问题的方法。四面体核酸框架(tFNAs)是新型纳米材料,由于其结构多样性,常被用作药物输送平台。本研究形成了 tFNAs-抗生素复合物(TAC),由于细菌对抗生素的吸收增加和药物穿过细胞膜的运动能力提高,TAC 对 和耐甲氧西林金黄色葡萄球菌(MRSA)具有很强的体外生长抑制作用。我们建立了全身性腹膜炎和局部伤口感染的小鼠模型。TAC 表现出良好的生物安全性,提高了严重感染小鼠的存活率,促进了局部感染的愈合。除了更好地将抗生素输送到靶标外,TAC 还可以通过调节 M1 和 M2 巨噬细胞的分化来增强免疫力,为治疗感染提供了新的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6cb/10069167/87ce06938b03/bm2c01525_0007_lrg.jpg
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