Cu<sub>2</sub>O/CuO-四环素复合材料的协同抑菌性能

吴迎花; 陈惠惠; 房迅; 季晓晖; 郭少波; 徐海涛; 李利华

doi:10.13801/j.cnki.fhclxb.20230417.004

Cu₂O/CuO-四环素复合材料的协同抑菌性能

doi: 10.13801/j.cnki.fhclxb.20230417.004

吴迎花^{1, 2,},
陈惠惠^{1, 2},
房迅^{1, 2},
季晓晖^{1, 2, ,},
郭少波^{1, 2, ,},
徐海涛^{1, 2},
李利华^{1, 2}

1.
陕西理工大学　化学与环境科学学院陕西省催化重点实验室，汉中 723001
2.
陕西理工大学　秦巴生物资源与生态环境国家重点实验室，汉中 723001

基金项目: 陕西省教育厅重点研究项目(21JS002)；陕西省教育厅科研项目(20JS017)；陕西省自然科学基金(2023-JC-QN-0162；2022JQ-148)；陕西省教育厅项目(22JK0311)；陕西理工大学基础研究基金(SLGKYXM2208)

详细信息

通讯作者:
季晓晖，博士，教授，硕士生导师，研究方向为天然产物提取和有机合成　E-mail: slgjxh@163.com

郭少波，硕士，讲师，研究方向为生物材料　E-mail: 545366954@qq.com

中图分类号: TB333
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出版历程
- 收稿日期: 2023-03-02
- 修回日期: 2023-04-04
- 录用日期: 2023-04-08
- 网络出版日期: 2023-04-17
- 刊出日期: 2023-12-01

Synergistic antibacterial study of Cu₂O/CuO-tetracycline composites

WU Yinghua^{1, 2
,},
CHEN Huihui^{1, 2},
FANG Xun^{1, 2},
JI Xiaohui^{1, 2
, ,},
GUO Shaobo^{1, 2
, ,},
XU Haitao^{1, 2},
LI Lihua^{1, 2}

1.
Shaanxi Key Laboratory of Catalysis, School of Chemical & Environment Science, Shaanxi University of Technology, Hanzhong 723001, China
2.
State Key Laboratory of Qinba Bio-Resource and Ecological Environment, Shaanxi University of Technology, Hanzhong 723001, China

Funds: Key Research Projects of the Education Department of Shaanxi Province (21JS002); Scientific Research Projects of the Education Department of Shaanxi Province (20JS017); Shaanxi Provincial Natural Science Foundation (2023-JC-QN-0162; 2022JQ-148); Shaanxi Provincial Department of Education Project (22JK0311); Fundamental Research Funds of Shaanxi University of Technology (SLGKYXM2208)

摘要

摘要: 耐药细菌快速的增长和新治疗策略的可用性越来越少，迫使人们急需研发出新型抑菌剂来解决这类难题。本文以三水硝酸铜[Cu(NO₃)₂·3H₂O]为原料、水合肼为还原剂制备氧化亚铜(Cu₂O/CuO)，通过与四环素配位结合得到Cu₂O/CuO-四环素复合材料。采用TEM、EDS、XRD、XPS、FTIR和UV-vis等表征技术对抑菌剂进行系统表征。探究了Cu₂O/CuO-四环素复合材料对革兰氏阳性菌金黄色葡萄球菌(S. aureus)、革兰氏阴性菌大肠杆菌(E. coli)和耐药菌沙门氏菌(T-Salmonella)的抑菌性能及抑菌机制。抑菌性能结果表明：抑菌浓度为150 µg/mL的Cu₂O/CuO-四环素复合材料在80 min时对E. coli、S. aureus和T-Salmonella的抑菌率均达到99.99%；与单独使用四环素和Cu₂O/CuO相比，Cu₂O/CuO-四环素复合材料对E. coli的抑菌效率分别提高了2.50和1.38倍，对S. aureus分别提高了1.58和1.18倍及对T-Salmonella分别提高1.26和1.12倍，总而言之，Cu₂O/CuO-四环素复合材料对E. coli最敏感。抑菌机制表明，该复合材料能有效破坏细菌细胞壁，使膜通透性发生改变，最终使细菌破裂死亡。Cu₂O/CuO-四环素复合材料具有优异的抑菌性能，进一步为公共卫生、生物医用等领域提供了广泛的科学依据。
- 医用 /
- Cu₂O/CuO /
- 四环素 /
- 复合材料 /
- 协同抑菌 /
- 抑菌机制
Abstract: The rapid growth of drug-resistant bacteria and the lack of availability of new treatment strategies make it urgent for people to develop new bacteriostatic agents to solve such problems. In this study, copper nitrate trihydrate [Cu(NO₃)₂·3H₂O] was used as a raw material and hydrazine hydrate as a reducing agent to prepare cuprous oxide (Cu₂O/CuO), then Cu₂O/CuO-tetracycline composites were obtained by combining them with tetracycline. Systematic characterization of inhibitors was conducted using TEM, XRD, XPS, FTIR, and UV-vis. The inhibitory properties and mechanism of Cu₂O/CuO-tetracycline on the Gram-positive bacterium Staphylococcus aureus (S. aureus), Gram-negative bacterium Escherichia coli (E. coli), and drug-resistant bacterium Salmonella (T-Salmonella) were studied. The results of antibacterial properties show that the antibacterial rate of Cu₂O/CuO-tetracycline composites with antibacterial concentration of 150 µg/mL to E. coli, S. aureus, and T-Salmonella reached 99.99% at 80 min. Compared with tetracycline and Cu₂O/CuO alone, the antibacterial efficiency of Cu₂O/CuO-tetracycline composite increase by 2.50 and 1.38 times for E. coli, 1.58 and 1.18 times for S. aureus and 1.26 and 1.12 times for T-Salmonella, respectively. In a word, Cu₂O/CuO-tetracycline composites are the most sensitive to E. coli. The antibacterial mechanism shows that the composite material can effectively destroy the bacterial cell wall, change the membrane permeability, and finally make the bacteria rupture and die. The Cu₂O/CuO-tetracycline composites have excellent antibacterial properties, indicating their wide application prospects in the fields of medical devices and medical materials.
- medical materials /
- Cu₂O/CuO /
- tetracycline /
- composite material /
- synergistic bacterial inhibition /
- bacteriostatic mechanism

HTML全文

图 1 Cu₂O/CuO-四环素复合物的合成示意图

Figure 1. Schematic of the synthesis of Cu₂O/CuO-tetracycline complexes

PVP—Polyvinylpyrrolidone

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图 2 Cu₂O/CuO的TEM图像

Figure 2. TEM images of Cu₂O/CuO

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图 3 (a) Cu₂O/CuO和Cu₂O/CuO-四环素的XRD图谱；Cu₂O/CuO-四环素复合材料中Cu2p (b)、C1s (c)、N1s (d) 和O1s (e) 的XPS图谱；(f) 四环素、Cu₂O/CuO和Cu₂O/CuO-四环素的FTIR图谱；(g) 光发射图谱(虚线)和Cu₂O/CuO-四环素和四环素的紫外可见吸收图谱(实线)

Figure 3. (a) XRD spectra of Cu₂O/CuO and Cu₂O/CuO-tetracycline; XPS spectra of Cu2p (b), C1s (c), N1s (d) and O1s (e) in Cu₂O/CuO-tetracycline composites; (f) FTIR spectra of tetracycline, Cu₂O/CuO and Cu₂O/CuO-tetracycline; (g) Photoemission spectra (dashed lines) and UV-vis absorption spectra (solid lines) of Cu₂O/CuO-tetracycline and tetracycline

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图 4 (a) 四环素和Cu₂O的优化电子结构和四环素的静电势(ESP)分析示意图；(b) Cu₂O与四环素的结合能

Figure 4. (a) Optimized electronic structure of tetracycline and Cu₂O and electrostatic potential (ESP) analysis diagram of tetracycline; (b) Binding Energy of Cu₂O with tetracycline

ΔG—Free energy

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图 5 不同浓度下四环素、Cu₂O/CuO和Cu₂O/CuO-四环素复合物对E. coli (a1)、S. aureus (b1) 和T-Salmonella (c1) 的滤纸扩散结果；抑菌圈直径随E. coli (a2)、S. aureus (b2) 和T-Salmonella (c2) 浓度变化的曲线

Figure 5. Filter paper diffusion results of tetracycline, Cu₂O/CuO and Cu₂O/CuO-tetracycline composites on E. coli (a1), S. aureus (b1) and T-Salmonella (c1) at different concentrations; Curves of the diameter of inhibition zone changing with concentration of E. coli (a2), S. aureus (b2) and T-Salmonella (c2)

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图 6 浓度为150 µg/mL的Cu₂O/CuO-四环素复合材料对E. coli (a)、S. aureus (b) 和T-Salmonella (c) 的菌落计数结果；(d) Cu₂O/CuO-四环素在不同时间对3种测试菌的抑菌率；(e) Cu₂O/CuO-四环素在不同时间对3种测试菌的菌落数；(f) 浓度为150 µg/mL的Cu₂O/CuO-四环素复合材料与3种测试菌混合5 min和40 min后的Zeta电位值

Figure 6. Colony counting results of E. coli (a), S. aureus (b) and T-Salmonella (c) by Cu₂O/CuO-tetracycline composites with concentration of 150 µg/mL; (d) Antibacterial rate of Cu₂O/CuO-tetracycline compound to three experimental bacteria in different time; (e) Colony number of Cu₂O/CuO-tetracycline composites to 3 kinds of tested bacteria in different time; (f) Zeta potential value of Cu₂O/CuO-tetracycline composites with concentration of 150 µg/mL mixed with 3 kinds of experimental bacteria for 5 min and 40 min

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图 7 (a) 电感耦合等离子体发射光谱法(ICP-OES)测得铜阳离子的累积释放；((b1)~(b3)) 空白对照组纯菌E. coli、S. aureus和T-Salmonella的代表性荧光图像；((b4)~(b6)) Cu₂O/CuO-四环素复合材料与E. coli、S. aureus和T-Salmonella接触2 h后的代表性荧光图像

Figure 7. (a) Cumulative release of copper cations measured by inductively coupled plasma optical emission spectrometer (ICP-OES); ((b1)-(b3)) Representative fluorescence images of pure bacteria E. coli, S. aureus and T-Salmonella in the blank control group;((b4)-(b6)) Representative fluorescence images of Cu₂O/CuO-tetracycline composite after contacting with E. coli, S. aureus and T-Salmonella for 2 h

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图 8 Cu₂O/CuO-四环素复合材料对革兰氏阴性菌的抑菌机制图

Figure 8. Bacteriostatic mechanism diagram of Cu₂O/CuO-tetracycline composite against Gram-negative bacteria

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