万古霉素修饰的硅包银纳米三角片在耐万古霉素肠球菌拉曼成像和光动力学抑菌治疗中的应用

doi:10.7503/cjcu20160758

高等学校化学学报 ›› 2017, Vol. 38 ›› Issue (5): 846.doi: 10.7503/cjcu20160758

万古霉素修饰的硅包银纳米三角片在耐万古霉素肠球菌拉曼成像和光动力学抑菌治疗中的应用

江婷婷(), 王远芳, 刘佩龙, 田义霞, 厉浩, 胡永国

鲁东大学生命科学学院, 烟台 264025

收稿日期:2016-11-01 出版日期:2017-05-10 发布日期:2017-04-20
作者简介:联系人简介: 江婷婷, 女, 博士, 讲师, 主要从事纳米生物材料及耐药抑菌药物研究. E-mail:jiangtingting@ldu.edu.cn
基金资助:
国家自然科学基金(批准号: 21505066)、山东省自然科学基金(批准号: ZR2014BP004)、教育部留学回国人员科研启动基金和鲁东大学人才引进启动基金(批准号: LY2013019)资助

Vancomycin Derivative Modified Silica-coated Silver Nanoplate for Surface-enhanced Raman Scattering Imaging and Antimicrobial Photodynamic Therapy of Vancomycin Resistant Bacterial Strains^†

JIANG Tingting^*(), WANG Yuanfang, LIU Peilong, TIAN Yixia, LI Hao, HU Yongguo

School of Life Sciences, Ludong University, Yantai 264025, China

Received:2016-11-01 Online:2017-05-10 Published:2017-04-20
Contact: JIANG Tingting E-mail:jiangtingting@ldu.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(No.21505066), the Natural Science Foundation of Shandong Province, China(No.ZR2014BP004), the Scientific Research Foundation for Returned Overseas Chinese Scholars, State Education Ministry of China and the Startup Foundation of Ludong University, China(No.LY2013019)

摘要/Abstract

摘要：

在银纳米三角片表面增强拉曼散射(SERS)活性基底表面包裹二氧化硅后再修饰卟啉-万古霉素单体化合物(Por-Van), 制备了功能化的复合纳米颗粒(AgNPl@SiO₂-Por-Van). 将该复合纳米颗粒用于耐万古霉素肠球菌(VRE)的拉曼成像和光动力学抑菌治疗. 结果表明, 该复合纳米颗粒能够与VRE耐药菌细胞壁间高效特异性结合, 并且其体外光动力学抑菌活性均显著优于卟啉和卟啉-万古霉素单体. 体外小鼠伤口感染实验进一步证实了其体内光动力学抑菌疗效. Por-Van修饰的复合纳米颗粒将拉曼成像和光动力学抑菌治疗有效整合, 作为一种新型诊疗系统, 可用于VRE耐药菌相关感染的监测及治疗.

关键词: 银纳米三角片, 表面增强拉曼散射成像, 光动力学抑菌治疗, 耐万古霉素肠球菌

Abstract:

Silver nanoplates, as SERS-active cores, were encapsulated by silica shell and modified with porphyrin-vancomycin(Por-Van) molecules to prepare AgNPl@SiO₂-Por-Van composite. The Por-Van molecules conjugated on the AgNPl@SiO₂ core/shell nanostructure were applied for surface enhanced raman scattering(SERS) detection and antimicrobial photodynamic therapy(aPDT) of Vancomycin resistant enterococci(VRE) strains. Results for in vitro bacterial SERS imaging revealed that the core/shell nanostructure highly enhanced specific binding affinity towards VRE bacteria. Meanwhile, excellent bactericidal effect was also obtained through in vitro and in vivo photodynamic therapy studies. Therefore, the AgNPl@SiO₂-Por-Van indicated high possibility for applications in theranostics towards VRE bacteria, integrating SERS imaging and aPDT.

Key words: Silver nanoplates(AgNPls), Surface-enhanced Raman scattering imaging, Antimicrobial photodynamic therapy(aPDT), Vancomycin resistant enterococci(VRE)

中图分类号:

O644

TrendMD:

江婷婷, 王远芳, 刘佩龙, 田义霞, 厉浩, 胡永国. 万古霉素修饰的硅包银纳米三角片在耐万古霉素肠球菌拉曼成像和光动力学抑菌治疗中的应用. 高等学校化学学报, 2017, 38(5): 846.

JIANG Tingting, WANG Yuanfang, LIU Peilong, TIAN Yixia, LI Hao, HU Yongguo. Vancomycin Derivative Modified Silica-coated Silver Nanoplate for Surface-enhanced Raman Scattering Imaging and Antimicrobial Photodynamic Therapy of Vancomycin Resistant Bacterial Strains^†. Chem. J. Chinese Universities, 2017, 38(5): 846.

图/表 11

Fig.1 Synthesis of AgNPl@SiO2-Por-Van

Fig.2 Structure and synthetic route of Por-Van

Fig.3 TEM images of AgNPls(A) and AgNPl@SiO2(B) and dynamic light scattering result of AgNPl@SiO2-Por-Van(C)

Fig.4 Raman spectra(A) and UV-Vis specta(B, C) of AgNPl@SiO2-Por-Van and relative moieties(C)

Fig.5 FTIR spectra of the Por-Van(a), AgNPl@SiO2(b) and AgNPl@SiO2-Por-Van(c)

Table 1 Minimum inhibition concentration(MIC) of AgNPl@SiO2-Por-Van and relative moieties towards Vancomycin sensitive and resistant bacterial strains

Sample	MIC/(μmol·L^-1)
Sample	B. Subtilis	E. Faecium	E. Faecalis
Van	1	>88	44
Por-Van	3	>15^*	>15^*
AgNPl@SiO₂-Por-Van	0.005	>0.010^*	>0.010^*

Fig.6 SERS(A1—C1) and the original Raman spectra(A2—C2) of five different points(A1)—(C1) Merged pictures of photographic images and Raman mappings of different bacterial strains. The maps are constructed on the band area at 1075 cm-1; (A2)—(C2) the Raman spectra in colors are collected from the points highlighted with same color by Raman confocal microscopy. (A1, A2) B. Subtilis; (B1, B2) E. Faecium(Van A); (C1, C2) E. Faecalis(Van B).

Fig.7 Dose(A, B) and light(C, D) dependent photodynamic inactivation effect of Por, Por-Van and AgNPl@SiO2-Por-Van towards E. faecium(VanA)(A, C) and E. faecalis(VanB)(B, D) (A, B) The irradiation time is 30 min; (B, D) the concentration is 10 nmol/L.

Fig.8 MTT assays for cytotoxicity and phototoxicity of AgNPl@SiO2-Por-Van Illumination time: 30 min.

Fig.9 Color photographs of infection sites(wounds created at the mice back) of animals from different experimental groups(A1)—(A5) Non-treated; (B1—B5) AgNPl@SiO2-Por-Van treated without illumination; (C1)—(C5) AgNPl@SiO2-Por-Van treated with illumination. Time/d: (A1—C1) 0; (A2—C2) 1; (A3—C3) 2; (A4—C4) 3; (A5—C5) 4.

Fig.10 Quantitification of bacterial infection after the in vivo aPDT treatment at the fourth daya. Non-treated; b. AgNPl@SiO2-Por-Van treated without illumination; c. AgNPl@SiO2-Por-Van treated with illumination.

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万古霉素修饰的硅包银纳米三角片在耐万古霉素肠球菌拉曼成像和光动力学抑菌治疗中的应用

Vancomycin Derivative Modified Silica-coated Silver Nanoplate for Surface-enhanced Raman Scattering Imaging and Antimicrobial Photodynamic Therapy of Vancomycin Resistant Bacterial Strains^†

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