光敏剂T1的光动力抗菌与抗肿瘤活性

doi:10.3969/j.issn.1000-1565.2019.05.013

摘要/Abstract

摘要： 为了探讨同种光敏剂对肿瘤细胞及耐药细菌的光动力(photodynamic therapy,PDT)治疗效果,体外选取了金黄色葡萄球耐药菌(methicillin-resistant Staphylococcus aureus, MRSA)及结肠癌细胞(CT-26),采用激光共聚焦显微镜检测MRSA及CT-26对半乳糖酞菁类光敏剂T1的吞噬,四甲基偶氮唑蓝染色法(MTT法)和菌落计数法检测T1对CT-26细胞和MRSA的光反应及暗反应浓度曲线;结果发现CT-26细胞及MRSA对T1吸收迅速且呈时间和浓度依赖性. T1介导的PDT对CT-26细胞和MRSA均具有较强的抑制,激光共聚焦显微镜也显示T1在CT-26细胞和MRSA内都有很强的荧光信号.T1介导的PDT能明显抑制MRSA及CT-26细胞的增殖,未来有可能成为一种治疗由细菌感染引起肿瘤的新方法,为PDT的临床应用提供实验数据.

关键词: 光敏剂, 光动力疗法, 细菌, 肿瘤细胞

Abstract: To investigate the photodynamic therapy(PDT)effect of the same photosensitivities on tumor cells and drug-resistant bacteria, colon cancer cells(CT-26)and methicillin-resistant Staphylococcus aureus(MRSA)selected in vitro. The phagocytosis of photosensitizer T1 by MRSA and CT-26 was detected by laser confocal microscopy. The light and dark response curves of T1 to CT-26 cells and MRSA were determined by MTT staining and colony counting. The results showed that both CT-26 cells and MRSA absorbed T1 rapidly in a time-dependent and concentration-dependent manner. T1-mediated PDT showed strong inhibition on CT-26 cells and MRSA, and CT-26 cells and MRSA showed strong fluorescence signal of T1 by confocal laser microscopy. The proliferation of MRSA and CT-26 cells were significantly inhibited through T1-mediated PDT, and PDT may become a new method for the treatment of tumors which caused by bacterial infection in the future, providing experimental data for the clinical application of PDT.- DOI:10.3969/j.issn.1000-1565.2019.05.013光敏剂T1的光动力抗菌与抗肿瘤活性赵占娟¹,马莹莹²,刘亚萌¹,杨焱惜¹,商亚贞³,赵建喜³(1. 河北大学医学院,河北保定 071002;2.河北大学公共卫生学院,河北保定 071002;3.河北大学附属医院放射科,河北保定 071002)摘要:为了探讨同种光敏剂对肿瘤细胞及耐药细菌的光动力(photodynamic therapy,PDT)治疗效果,体外选取了金黄色葡萄球耐药菌(methicillin-resistant Staphylococcus aureus, MRSA)及结肠癌细胞(CT-26),采用激光共聚焦显微镜检测MRSA及CT-26对半乳糖酞菁类光敏剂T1的吞噬,四甲基偶氮唑蓝染色法(MTT法)和菌落计数法检测T1对CT-26细胞和MRSA的光反应及暗反应浓度曲线;结果发现CT-26细胞及MRSA对T1吸收迅速且呈时间和浓度依赖性. T1介导的PDT对CT-26细胞和MRSA均具有较强的抑制,激光共聚焦显微镜也显示T1在CT-26细胞和MRSA内都有很强的荧光信号.T1介导的PDT能明显抑制MRSA及CT-26细胞的增殖,未来有可能成为一种治疗由细菌感染引起肿瘤的新方法,为PDT的临床应用提供实验数据.关键词:光敏剂;光动力疗法;细菌;肿瘤细胞中图分类号:R735 文献标志码:A 文章编号:1000-1565(2019)05-0522-07Photodynamic antibacterial and antitumor activity of photosensitizer T1ZHAO Zhanjuan¹, MA Yingying², LIU Yameng¹, YANG Yanxi¹, SHANG Yazhen³, ZHAO Jianxi³(1. College of Basic Medical Science, Hebei University, Baoding 071002, China;2. College of Public Health, Hebei University, Baoding 071002, China;3. Department of Radiology, Affiliated Hospital of Hebei University, Baoding 071002, China)Abstract: To investigate the photodynamic therapy(PDT)effect of the same photosensitivities on tumor cells and drug-resistant bacteria, colon cancer cells(CT-26)and methicillin-resistant Staphylococcus aureus(MRSA)selected in vitro. The phagocytosis of photosensitizer T1 by MRSA and CT-26 was detected by laser confocal microscopy. The light and dark response curves of T1 to CT-26 cells and MRSA were determined by MTT staining and colony counting. The results showed that both CT-26 cells and MRSA absorbed T1 rapidly in a time-dependent and concentration-dependent manner. T1-mediated PDT showed strong inhibition on CT-26 cells and MRSA, and CT-26 cells and MRSA showed strong fluorescence signal of T1 by confocal laser microscopy. The proliferation of MRSA and CT-26 cells were significantly inhibited through T1-mediated PDT, and PDT may become a new method for the treatment of tumors which caused by bacterial infection in the future, providing experimental data for the clinical application of PDT.- 收稿日期:2019-03-04 基金项目:河北省卫生厅资助项目(20170833);河北大学大学生创新训练计划项目(2018307;2019027);河北大学医学院2018年实验室开放项目第一作者:赵占娟(1974—),女,河北博野人,河北大学副教授,博士,主要从事激光医学方向研究. E-mail:zhaozhanjuanv@163.com 通信作者:赵建喜(1969—),男,河北保定人,河北大学教授,主要从事影像诊断方向研究.E-mail:jianxizhaov@163.com第5期赵占娟等:光敏剂T1的光动力抗菌与抗肿瘤活性

Key words: photosensitizer, photodynamic therapy, bacteria, tumor cell

中图分类号:

R735

赵占娟,马莹莹,刘亚萌,杨焱惜,商亚贞,赵建喜. 光敏剂T1的光动力抗菌与抗肿瘤活性[J]. 河北大学学报(自然科学版), 2019, 39(5): 522-528.

ZHAO Zhanjuan, MA Yingying, LIU Yameng, YANG Yanxi, SHANG Yazhen, ZHAO Jianxi. Photodynamic antibacterial and antitumor activity of photosensitizer T1[J]. Journal of Hebei University (Natural Science Edition), 2019, 39(5): 522-528.

参考文献

[1] LI X S, KOLEMEN S, YOON J, et al. Activatable photosensitizers: agents for selective photodynamic therapy[J]. Advanced Functional Materials, 2017, 27(5): 1604053. DOI:10.1002/adfm.201604053.
[2] LIU J H, JIN L H, WANG Y H, et al. A new Co-P nanocomposite with ultrahigh relaxivity for in vivo magnetic resonance imaging-guided tumor eradication by chemo/photothermal synergistic therapy[J]. Small, 2018, 14(7): 1702431. DOI:10.1002/smll.201702431.
[3] ORMOND A, FREEMAN H. Dye sensitizers for photodynamic therapy[J]. Materials, 2013, 6(3): 817-840. DOI:10.3390/ma6030817.
[4] GONG H, CHAO Y, XIANG J, et al. Hyaluronidase to enhance nanoparticle-based photodynamic tumor therapy[J]. Nano Letters, 2016, 16(4): 2512-2521. DOI:10.1021/acs.nanolett.6b00068.
[5] TAVARES A, CARVALHO C M B, FAUSTINO M A, et al. Antimicrobial photodynamic therapy: study of bacterial recovery viability and potential development of resistance after treatment[J]. Marine Drugs, 2010, 8(1): 91-105. DOI:10.3390/md8010091.
[6] 葛伟颖. 激光光动力诊断早期结肠癌的分子影像学研究[D]. 保定: 河北大学, 2017.
[7] FU X J, FANG Y, YAO M. Antimicrobial photodynamic therapy for methicillin-resistant Staphylococcus aureus infection[J]. BioMed Research International, 2013, 2013: 1-9. DOI:10.1155/2013/159157.
[8] MAISCH T. Resistance in antimicrobial photodynamic inactivation of bacteria[J]. Photochemical & Photobiological Sciences, 2015, 14(8): 1518-1526. DOI:10.1039/c5pp00037h.
[9] CEYHAN T, ALTÌNDAL A, ÖZKAYA A R, et al. Novel ball-type four dithioerythritol bridged metallophthalocyanines and their water-soluble derivatives: Synthesis and characterization, and electrochemical, electrocatalytic, electrical and gas sensing properties[J]. Dalton Transactions, 2010, 39(41): 9801. DOI:10.1039/c0dt00641f.
[10] LI X S, ZHENG B D, PENG X H, et al. Phthalocyanines as medicinal photosensitizers: Developments in the last five years[J]. Coordination Chemistry Reviews, 2019, 379: 147-160. DOI:10.1016/j.ccr.2017.08.003.
[11] 孔懿, 徐虹, 乔浦, 等. 金黄色葡萄球耐药菌引起的医院内获得性抗生素相关性腹泻[J]. 中华医院感染学杂志, 2018, 28(9): 1420-1423, 1428. DOI:10.11816/cn.ni.2018-180104.
[12] SPESIA M B, CAMINOS D A, PONS P, et al. Mechanistic insight of the photodynamic inactivation of Escherichia coli by a tetracationic zinc(II)phthalocyanine derivative[J]. Photodiagnosis and Photodynamic Therapy, 2009, 6(1): 52-61. DOI:10.1016/j.pdpdt.2009.01.003.
[13] 席清平. 五倍子水提取物对菌斑生物膜影响的体外研究[D]. 西安: 第四军医大学, 2004.
[14] 曹波. 新型水溶性光敏剂的评价和机制研究[D]. 北京:北京协和医学院, 2012.
[15] 邵红霞, 刘蓉, 吴琦, 等. 光敏剂在光动力疗法中的作用[J]. 医学综述, 2008, 14(22): 3404-3407. DOI:10.3969/j.issn.1006-2084.2008.22.016.
[16] 聂修红. 酞菁类光敏剂的设计、合成及其活性测试[D]. 武汉: 武汉工程大学, 2017.
[17] 韩瑞, 曹景玉, 姜海涛, 等. 血卟啉光动力对人胆管癌细胞转移潜能影响实验研究[J]. 中华肿瘤防治杂志, 2014, 21(2):113-117.DOI:10.3969/j.issn.1673-5269.2014.02.008.