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基于氨基酸配位自组装的多功能抗菌生物金属水凝胶

Multifunctional Antimicrobial Biometallohydrogels Based on Amino Acid Coordinated Self-Assembly.

机构信息

State Key Laboratory of Metastable Materials Science and Technology, Yanshan University, Qinhuangdao, 066004, P. R. China.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

出版信息

Small. 2020 Feb;16(8):e1907309. doi: 10.1002/smll.201907309. Epub 2020 Jan 29.

Abstract

There is a real need for new antibiotics against self-evolving bacteria. One option is to use biofriendly broad-spectrum and mechanically tunable antimicrobial hydrogels that can combat multidrug-resistant microbes. Whilst appealing, there are currently limited options. Herein, broad-spectrum antimicrobial biometallohydrogels based on the self-assembly and local mineralization of Ag -coordinated Fmoc-amino acids are reported. Such biometallohydrogels have the advantages of localized delivery and sustained release, reduced drug dosage and toxicity yet improved bioavailability, prolonged drug effect, and tunable mechanical strength. Furthermore, they can directly interact with the cell walls and membrane, resulting in the detachment of the plasma membrane and leakage of the cytoplasm. This leads to cell death, triggering a significant antibacterial effect against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria in cells and mice. This study paves the way for developing a multifunctional integration platform based on simple biomolecules coordinated self-assembly toward a broad range of biomedical applications.

摘要

针对具有自我进化能力的细菌,我们急需开发新型抗生素。其中一个选择是使用对生物友好的广谱且机械可调的抗菌水凝胶,以对抗多种耐药微生物。虽然这很有吸引力,但目前的选择有限。在此,我们报告了基于 Ag 配位 Fmoc-氨基酸自组装和局部矿化的广谱抗菌生物金属水凝胶。这种生物金属水凝胶具有局部递送和持续释放、减少药物剂量和毒性、提高生物利用度、延长药物作用时间以及可调机械强度的优点。此外,它们可以直接与细胞壁和细胞膜相互作用,导致质膜脱落和细胞质泄漏。这会导致细胞死亡,从而对细胞和小鼠中的革兰氏阴性(大肠杆菌)和革兰氏阳性(金黄色葡萄球菌)细菌产生显著的抗菌作用。本研究为基于简单生物分子配位自组装开发多功能集成平台铺平了道路,可应用于广泛的生物医学领域。

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