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生物膜微环境响应型聚合物 CO 释放胶束提高阿米卡星疗效

Biofilm microenvironment-responsive polymeric CO releasing micelles for enhanced amikacin efficacy.

机构信息

Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an, Shaanxi 710072, PR China.

Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE) & Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an, Shaanxi 710072, PR China.

出版信息

J Control Release. 2023 May;357:561-571. doi: 10.1016/j.jconrel.2023.04.025. Epub 2023 Apr 21.

DOI:10.1016/j.jconrel.2023.04.025
PMID:37076015
Abstract

Biofilm-associated infections (BAI) have posed serious threats to public health. Novel therapy based on carbon monoxide (CO) is being increasingly appreciated. However, CO therapy like inhaled gas treatment was impeded owing to its low bioavailability. Besides, the direct use of CO releasing molecules (CORM) showed low therapeutic efficacy in BAI. Therefore, it is vital to improve the efficiency of CO therapy. Herein, we proposed polymeric CO releasing micelles (pCORM) from self-assembly of amphiphilic copolymers containing CORM bearing block as hydrophobic part and acryloylmorpholine block as hydrophilic part. The catechol modified CORM were conjugated through pH cleavable boronate ester bonds and releasing CO passively under biofilm microenvironment. When combined with subminimal inhibitory concentration antibiotic amikacin, pCORM could significantly enhance its bactericidal efficiency against biofilm-encapsulated multidrug-resistant bacteria, representing a promising approach to combat BAI.

摘要

生物膜相关感染 (BAI) 对公共健康构成了严重威胁。基于一氧化碳 (CO) 的新型疗法越来越受到重视。然而,由于 CO 的生物利用度低,像吸入气体治疗等 CO 疗法受到了阻碍。此外,直接使用 CO 释放分子 (CORM) 在 BAI 中的治疗效果不佳。因此,提高 CO 疗法的效率至关重要。在这里,我们提出了一种由含有 CO 释放体的两亲性嵌段共聚物自组装而成的聚合物 CO 释放胶束 (pCORM),其中 CO 释放体作为疏水性部分,丙烯酰吗啉嵌段作为亲水性部分。通过 pH 可裂解的硼酸酯键将儿茶酚修饰的 CORM 连接起来,并在生物膜微环境中被动释放 CO。当与亚最小抑菌浓度的抗生素阿米卡星联合使用时,pCORM 可以显著提高其对生物膜包裹的多重耐药菌的杀菌效率,为治疗 BAI 提供了一种有前途的方法。

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