|
|
|
| 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 |
|
|
|
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.
|
|
Received: 02 November 2016
Published: 07 August 2017
|
|
Corresponding Authors:
TANG Guping
E-mail: liuxg@zju.edu.cn;tangguping@zju.edu.cn
|
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
|
|
| [1] |
CHENG L , WANG C , FENG L et al. Functional nanomaterials for phototherapies of cancer[J]. Chem Rev, 2014, 114 (21): 10869- 10939
doi: 10.1021/cr400532z
|
|
|
| [2] |
LUCKY S S , SOO K C , ZHANG Y . Nanoparticles in photodynamic therapy[J]. Chem Rev, 2015, 115 (4): 1990- 2042
doi: 10.1021/cr5004198
|
|
|
| [3] |
LI W , PENG J , TAN L et al. Mild photothermal therapy/photodynamic therapy/chemotherapy of breast cancer by Lyp-1 modified Docetaxel/IR820 Co-loaded micelles[J]. Biomaterials, 2016, 106 119- 133
doi: 10.1016/j.biomaterials.2016.08.016
|
|
|
| [4] |
KAMKAEW A , LIM S H , LEE H B et al. BODIPY dyes in photodynamic therapy[J]. Chem Soc Rev, 2013, 42 (1): 77- 88
doi: 10.1039/C2CS35216H
|
|
|
| [5] |
KE M R , YEUNG S L , NG D K et al. Preparation and in vitro photodynamic activities of folate-conjugated distyryl boron dipyrromethene based photosensitizers[J]. J Med Chem, 2013, 56 (21): 8475- 8483
doi: 10.1021/jm4009168
|
|
|
| [6] |
LOUDET A , BURGESS K . BODIPY dyes and their derivatives: syntheses and spectroscopic properties[J]. Chem Rev, 2007, 107 (11): 4891- 4932
doi: 10.1021/cr078381n
|
|
|
| [7] |
YOGO T , URANO Y , MIZUSHIMA A et al. Selective photoinactivation of protein function through environment-sensitive switching of singlet oxygen generation by photosensitizer[J]. Proc Natl Acad Sci U S A, 2008, 105 (1): 28- 32
doi: 10.1073/pnas.0611717105
|
|
|
| [8] |
WANG S , LIU H , MACK J et al. A BODIPY-based'turn-on'fluorescent probe for hypoxic cell imaging[J]. Chem Commun, 2015, 51 (69): 13389- 13392
doi: 10.1039/C5CC05139H
|
|
|
| [9] |
LIM S H , THIVIERGE C , NOWAK-SLIWINSKA P et al. In vitro and in vivo photocytotoxicity of boron dipyrromethene derivatives for photodynamic therapy[J]. J Med Chem, 2010, 53 (7): 2865- 2874
doi: 10.1021/jm901823u
|
|
|
| [10] |
李 黎波 , 李 文敏 , 项 蕾红 et al. 光动力疗法在中国的应用与临床研究[J]. 中国激光医学杂志, 2012, 21 (5): 278- 307
LI Libo , LI Wenming , XIANG Leihong et al. Photodynamic therapy: clinical research and application in China[J]. Chinese Journal of Laser Medicine & Surgery, 2012, 21 (5): 278- 307
|
|
|
| [11] |
HE H , LO P C , YEUNG S L et al. Synthesis and in vitro photodynamic activities of pegylated distyryl boron dipyrromethene derivatives[J]. J Med Chem, 2011, 54 (8): 3097- 3102
doi: 10.1021/jm101637g
|
|
|
| [12] |
BOURRé L , THIBAUT S , BRIFFAUD A et al. Indirect detection of photosensitizer ex vivo[J]. J Photochem Photobiol B, 2002, 67 (1): 23- 31
doi: 10.1016/S1011-1344(02)00279-8
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
