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用于按需释放生物膜分散酶以有效根除口腔生物膜的壳聚糖-链霉素共轭物的溶菌酶响应水凝胶

Lysozyme-Responsive Hydrogels of Chitosan-Streptomycin Conjugates for the On-Demand Release of Biofilm-Dispersing Enzymes for the Efficient Eradication of Oral Biofilms.

作者信息

Del Pozo María Luisa, Aguanell Antonio, García-Junceda Eduardo, Revuelta Julia

机构信息

BioGlycoChem Group, Departamento de Química Bio-Orgánica, Instituto de Química Orgánica General, CSIC (IQOG-CSIC), Juan de la Cierva 3, Madrid 28006, Spain.

出版信息

Chem Mater. 2024 Sep 30;36(19):9860-9873. doi: 10.1021/acs.chemmater.4c02014. eCollection 2024 Oct 8.

Abstract

Hydrogels with controlled degradation and sustained antibiofilm activity are promising biomaterials for the treatment of oral infections such as periodontitis or caries. In this article, an forming chitosan-streptomycin hydrogel is developed that can target established bacterial biofilms in response to lysozyme, an enzyme that is overexpressed in saliva during oral infections. When the new hydrogel is applied to simulated oral biofilms, the overexpressed lysozyme degrades the hydrogel and releases chitosan-streptomycin oligosaccharides that can eradicate the biofilm. This work has shown that the coupling of chitosan and streptomycin can have a synergistic effect and that the new hydrogel based on chitosan-streptomycin conjugate can effectively combat biofilms of , , and formed achieving a significant reduction in the biomass of the biofilm and a substantial reduction in the population of viable bacteria in established biofilms. Finally, the CS-Str hydrogel loaded with biofilm-disrupting enzymes, in particular, DNase I and/or DspB, showed a significantly increased ability to reduce the biofilm biomass of and (by over 84% and up to 92%, respectively), resulting in a drastic reduction in cell viability, which fell below 4% for and below 5% for .

摘要

具有可控降解和持续抗生物膜活性的水凝胶是治疗牙周炎或龋齿等口腔感染的有前景的生物材料。在本文中,开发了一种形成壳聚糖-链霉素的水凝胶,它可以响应溶菌酶靶向已形成的细菌生物膜,溶菌酶是一种在口腔感染期间唾液中过度表达的酶。当将这种新型水凝胶应用于模拟口腔生物膜时,过度表达的溶菌酶会降解水凝胶并释放壳聚糖-链霉素寡糖,从而根除生物膜。这项工作表明壳聚糖和链霉素的偶联可以产生协同效应,并且基于壳聚糖-链霉素共轭物的新型水凝胶可以有效对抗由 、 和 形成的生物膜,使生物膜的生物量显著减少,已形成生物膜中的活菌数量大幅降低。最后,负载有生物膜破坏酶(特别是DNase I和/或DspB)的CS-Str水凝胶显示出显著提高的减少 和 生物膜生物量的能力(分别超过84%和高达92%),导致细胞活力急剧下降, 细胞活力降至4%以下, 细胞活力降至5%以下。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50b/11468777/c86d5c76278b/cm4c02014_0009.jpg

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