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溶菌酶偶联的 Ag.ZnO@HA 纳米复合材料的合成与表征:一种具有光催化活性的氧化还原和 pH 响应型抗菌剂。

Synthesis and characterization of lysozyme-conjugated Ag.ZnO@HA nanocomposite: A redox and pH-responsive antimicrobial agent with photocatalytic activity.

机构信息

Biochemical Research center, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, P. O. Box 9177948974, Mashhad, Iran.

Biochemical Research center, Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, P. O. Box 9177948974, Mashhad, Iran; Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.

出版信息

Photodiagnosis Photodyn Ther. 2021 Sep;35:102418. doi: 10.1016/j.pdpdt.2021.102418. Epub 2021 Jun 29.

DOI:10.1016/j.pdpdt.2021.102418
PMID:34197967
Abstract

Hydroxyapatite (HA) is extensively used for implantable device coating; however, it lacks antibacterial property, leading to potential bacterial infection during orthopedic implantation surgery. Herein, to enhance the antibacterial activity of HA, a redox- and pH-responsive HA nanocomposite with photocatalytic activity was designed. A photosensitive heterostructure, zinc oxide/hydroxyapatite (ZnO.HA), was coated with Ag nanoparticles (AgNPs) with assisted gallic acid using the UV-irradiation method. An antibacterial enzyme, lysozyme, was then conjugated on the surface of the nanocomposite by a cleavable disulfide linker, resulting in a redox-sensitive nanoplatform. In comparison with bare HA, the designed nanocomposites as Lyso.CAGZ@HA displayed much higher antibacterial activity (> 5-fold) toward Escherichia coli (E. coli) owing to the synergistic antibacterial effects of ZnONPs, AgNPs, gallic acid, and lysozyme on the surface of the nanocomposite. However, antibacterial and antifouling effects are much more enhanced in Lyso.CAGZ@HA-treated bacteria as they were subjected to UVA irradiation. Moreover, the cellular uptake of nanocomposite and intracellular glutathione depletion enhanced in the presence of UVA light, resulting in reactive oxygen specious generation enhancement. Further, in vitro cytotoxicity experiments on mammalian cells (human foreskin fibroblast) revealed that nanocomposite has no cytotoxic effects. Hence, this study demonstrated that Lyso.CAGZ@HA could be considered as a potential therapeutic approach against bacterial infectious diseases.

摘要

羟基磷灰石(HA)被广泛用于可植入设备的涂层;然而,它缺乏抗菌性能,导致在骨科植入手术中存在潜在的细菌感染风险。在此,为了增强 HA 的抗菌活性,设计了一种具有光催化活性的氧化还原和 pH 响应的 HA 纳米复合材料。使用紫外光照射法,在氧化锌/羟基磷灰石(ZnO.HA)光敏异质结构上涂覆了带有辅助没食子酸的银纳米颗粒(AgNPs)。然后,通过可裂解的二硫键连接物将抗菌酶溶菌酶接枝到纳米复合材料表面,形成氧化还原敏感的纳米平台。与裸 HA 相比,设计的纳米复合材料 Lyso.CAGZ@HA 对大肠杆菌(E. coli)的抗菌活性(>5 倍)更高,这是由于 ZnONPs、AgNPs、没食子酸和溶菌酶在纳米复合材料表面的协同抗菌作用。然而,在 Lyso.CAGZ@HA 处理的细菌中,由于 UVA 照射,其抗菌和抗污效果得到了极大增强。此外,在存在 UVA 光的情况下,纳米复合材料的细胞摄取和细胞内谷胱甘肽耗竭增强,导致活性氧种类生成增强。进一步,对哺乳动物细胞(人包皮成纤维细胞)的体外细胞毒性实验表明,纳米复合材料没有细胞毒性。因此,本研究表明 Lyso.CAGZ@HA 可以被认为是一种潜在的治疗细菌感染性疾病的方法。

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