四苯乙烯骨架的光动力学治疗试剂合成及体外抗肿瘤活性

doi:10.3969/j.issn.1000-1565.2025.02.008

河北大学学报(自然科学版) ›› 2025, Vol. 45 ›› Issue (2): 176-184.DOI: 10.3969/j.issn.1000-1565.2025.02.008

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四苯乙烯骨架的光动力学治疗试剂合成及体外抗肿瘤活性

房可欣,刘海通,王书香

收稿日期:2024-11-01 发布日期:2025-03-26
通讯作者: 王书香(1965—)
作者简介:房可欣(1999—),男,河北大学在读硕士研究生,主要从事抗肿瘤药物研究. E-mail:472415134@qq.com
基金资助:
国家自然科学基金资助项目(22177026)

Synthesis and in vitro antitumor activity of photodynamic therapy reagent based on tetraphene skeleton

FANG Kexin, LIU Haitong, WANG Shuxiang

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis Ministry of Education, College of Chemistry and Materials Science, Hebei University, Baoding 071000, China

Received:2024-11-01 Published:2025-03-26

摘要/Abstract

摘要： 以4-溴二苯甲酮、4,4'-二甲氧基二苯甲酮、对硝基苄溴(Br-BNO₂)和叠氮基乳糖(LT)等为原料,经亲核取代、铃木偶联和click反应等构建了一种四苯乙烯(TPE)为骨架,并能高效产生活性氧(ROS)的光动力学治疗(PDT)试剂LT-TPE-DB-BNO₂. 采用分光光度法和共聚焦荧光显微镜探究LT-TPE-DB-BNO₂在血清和不同pH值溶液中的稳定性及细胞内外产生ROS的能力;利用MTT法和活死细胞双染法测定其对HeLa与BRL-3A细胞活力的影响. 结果表明: 在不同pH值溶液及血清中LT-TPE-DB-BNO₂表现出优良的稳定性;在黑暗条件下,LT-TPE-DB-BNO₂对HeLa和BRL-3A细胞的活力影响很小;在氙灯辐照下,LT-TPE-DB-BNO₂高效产生ROS,使HeLa细胞的活力下降88.3%,表明LT-TPE-DB-BNO₂是高效的PDT试剂.

关键词: 四苯乙烯骨架, 光动力学治疗试剂, 抗肿瘤活性

Abstract: A photodynamic therapy(PDT)reagent, LT-TPE-DB-BNO₂ for reactive oxygen species(ROS)generation based on tetraphene(TPE), was synthesized from 4-bromobenzoylbenzene, 4,4’-dimethoxybenzophenone, p-nitrobenzyl bromide(Br-BNO₂)and azide lactose(LT)by nucleophilic substitution, suzuki coupling and click reaction. The stability of LT-TPE-DB-BNO₂ in serum and at different pH value, and the ability of ROS generation were investigated by spectrophotometry and confocal fluorescence microscopy. The effects of LT-TPE-DB-BNO₂ on the viability of HeLa and BRL-3A cells were investigated by MTT method and live and dead cell double staining method. The results showed that LT-TPE-DB-BNO₂ was stable in serum and at different pH value. In the dark condition,it had a little effect on the activity of HeLa and BRL-3A cells. Under irradiation by xenon lamp, ROS was produced by LT-TPE-DB-BNO₂, and the activity of HeLa cells was reduced by 88.3%, indicating that LT-TPE-DB-BNO₂ is a highly efficient PDT reagent.

Key words: tetraphene skeleton, photodynamic therapy(PDT)reagent, antitumor activity

中图分类号:

O632.6

房可欣,刘海通,王书香. 四苯乙烯骨架的光动力学治疗试剂合成及体外抗肿瘤活性[J]. 河北大学学报(自然科学版), 2025, 45(2): 176-184.

FANG Kexin, LIU Haitong, WANG Shuxiang. Synthesis and in vitro antitumor activity of photodynamic therapy reagent based on tetraphene skeleton[J]. Journal of Hebei University(Natural Science Edition), 2025, 45(2): 176-184.

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四苯乙烯骨架的光动力学治疗试剂合成及体外抗肿瘤活性

Synthesis and in vitro antitumor activity of photodynamic therapy reagent based on tetraphene skeleton

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