生物正交点击-释放反应对碘代氟硼荧光动力探针的调控研究  

Bioorthogonal click-to-release reaction for regulating iodo-BODIPY PDT probe

作　　者：于欣煜 李杰[1] 李越 王雅乐 石维 吴昊星[1] YU Xin-yu;LI Jie;LI Yue;WANG Ya-yue;SHI Wei;WU Hao-xing(Huaxi MR Research Center,West China Hospital,Sichuan University,Chengdu 610041,China;Research Core Facility of West China Hospital,Sichuan University,Chengdu 610041,China;Institute of Drug Clinical Trial·GCP,West China Second University Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院临床磁共振研究中心,四川成都610041 [2]四川大学华西医院公共实验技术平台,四川成都610041 [3]四川大学华西第二医院国家药物临床试验机构,四川成都610041

出　　处：《药学学报》2023年第11期3400-3407,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(21977075);四川大学华西医院学科卓越发展1·3·5工程项目资助(ZYYC08004)。

摘　　要：本文合成构建了六种四嗪-氟硼荧(dipyrromethene boron difluoride,BODIPY)探针,并通过四嗪生物正交点击-释放反应实现了对探针单线态氧产率的高达14倍的调控,通过研究探针中不同四嗪取代基结构、meso-位不同羧基类型的探针光动力治疗(photodynamic therapy,PDT)性质,揭示了构效关系。通过对探针的稳定性和释放效率的筛选,获得了适用于活细胞应用的光动力探针P5、P6。该策略对四嗪及BODIPY官能团具有良好兼容性,扩大了四嗪生物正交点击-释放反应的应用范围,为BODIPY光动力探针的单线态氧产率调控提供了新思路。In this study,we synthesized six tetrazine-dipyrromethene boron difluoride(BODIPY)probes and achieved a remarkable up to 14-fold increase in singlet oxygen yield via tetrazine bioorthogonal click-to-release reactions.We systematically investigated the photodynamic activity of these probes,revealing crucial structureactivity relationships.Additionally,we evaluated the stability and release kinetics of these probes and identified P5 and P6 as ideal candidates for photodynamic therapy in live cells.This innovative strategy opens new avenues for fine-tuning the photodynamic properties of BODIPY dyes,thereby expanding their utility in cancer therapy.

关 键 词：光动力探针 生物正交反应 氟硼荧 点击-释放反应 四嗪 

分 类 号：R914[医药卫生—药物化学]