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J Zhejiang Univ (Med Sci)  2017, Vol. 46 Issue (2): 135-143    DOI: 10.3785/j.issn.1008-9292.2017.04.04
    
Synthesis of BODIPY photosensitizers and their photodynamic effect on cancer cells
LIU Xingang(),WU Min,LI Suying,Li Zhongbao,HU Qinglian,ZHOU Jun,TANG Guping*()
Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310003, China
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Abstract  

Objective: To design and synthesize photosensitizers with different substituents and to identify its physicochemical characteritics and photodynamic effect on cancer cells. Methods: Two kinds of BODIPY photosensitizers BPOI and BPCI were synthesized through condensation reaction between aldehyde and reactive hydrogen of pyrrole, followed with electrophilic substitution reaction. Physicochemical properties were characterized by 1H NMR, FT-IR and UV-visible absorption spectra and fluorescence emission spectra. The ability to produce reactive oxygen species was detected by BPDF and DCFH-DA. Photodynamic therapy effect on rat glioma C6 cells in vitro was determined by MTT method. Results: Two kinds of BODIPY photosensitizers BPOI and BPCI were successfully synthesized with different substituents, which were confirmed by 1H NMR, FT-IR. Both materials had low toxicity and could be readily taken up by tumor cells. The ability of synthesized photosensitizers to produce reactive oxygen species was strongly influenced by solvent polarity when the substituent was electron-donating group, while no effect was found when the substituent was electron-withdrawing group. Conclusion: Photosensitizer BPOI with electron-donating substituent produces reactive oxygen species with a slow rate in a highly polar environment, while greatly enhanced this effect in a low polarity environment, which is expected to be used for environmental-selective photodynamic therapy in tumor cells.



Key wordsPhotochemotherapy      Photosensitizing agents/pharmacokinetics      Photosensitizing agents/therapeutic use      Neoplasms/therapy      Tumor cells, cultured/drug effects      Spectrometry, fluorescence      Spectrum analysis      Pyrroles/pharmacology     
Received: 02 November 2016      Published: 07 August 2017
Corresponding Authors: TANG Guping     E-mail: liuxg@zju.edu.cn;tangguping@zju.edu.cn
Cite this article:

LIU Xingang,WU Min,LI Suying,Li Zhongbao,HU Qinglian,ZHOU Jun,TANG Guping. Synthesis of BODIPY photosensitizers and their photodynamic effect on cancer cells. J Zhejiang Univ (Med Sci), 2017, 46(2): 135-143.

URL:

http://www.zjujournals.com/xueshu/med/10.3785/j.issn.1008-9292.2017.04.04     OR     http://www.zjujournals.com/xueshu/med/Y2017/V46/I2/135


氟硼二吡咯类光敏剂的制备及对肿瘤细胞的光动力学影响

目的:设计合成两种不同极性取代基的氟硼二吡咯类光敏剂,观察其理化特性和在不同极性条件下的光动力学效应。方法:通过苯甲醛与吡咯活泼氢的缩合反应以及亲电取代反应制备氟硼二吡咯类光敏剂碘代羟基氟硼二吡咯(BPOI)和碘代甲酸甲酯氟硼二吡咯(BPCI)。通过核磁共振氢谱、傅里叶红外光谱和紫外可见吸收光谱、荧光发射光谱对该光敏剂进行理化性质表征。通过1,3-二苯基异苯并呋喃与2',7'-二氯荧光黄双乙酸盐检测该光敏剂活性氧产生能力,并采用MTT法检测其对肿瘤细胞的光动力学效应。结果:核磁共振氢谱和傅里叶红外光谱证实成功合成了两种不同取代基的氟硼二吡咯类光敏剂BPOI和BPCI。两种材料具有低毒性,且易被细胞摄取。meso位为给电子取代基的氟硼二吡咯类光敏剂BPOI产生活性氧的能力受溶剂极性影响大,而meso位为吸电子取代基的氟硼二吡咯类光敏剂BPCI则不受溶剂极性影响。结论:给电子取代基的氟硼二吡咯类光敏剂BPOI在高极性环境中产生活性氧速率慢,而在低极性环境中产生活性氧的能力大大增强,有望用于肿瘤细胞内的环境选择性光动力治疗。


关键词: 光化学疗法,  光敏感药/药代动力学,  光敏感药/治疗应用,  肿瘤/治疗,  肿瘤细胞,培养的/药物作用,  光谱法,荧光,  光谱分析,  吡咯类/药理学 
Fig 1 Synthesis of photosensitizer BPOI and BPCI
Fig 2 1H NMR spectra of BPO, BPC and BPOI, BPCI
Fig 3 FT-IR spectra of BPOI and BPCI
Fig 4 UV-Vis absorption and fluorescence emission spectras of BPO, BPI, BPOI and BPOI in DMSO
Fig 5 CLSM images of C6 cells incubated with BPOI or BPCI for 4 h
Fig 6 Absorbance of DPBF in different solvent with BPOI or BPCI
Fig 7 Comparison of the absorbance intensity of DPBF in 415 nm
Fig 8 CLSM images of producing 1O2 in C6 cells incubated with BPOI and BPCI detected by DCFH-DA as tracer agent
Fig 9 Cell viability of C6 cells incubated with BPOI and BPCI with or without light by MTT assay
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