摘要
基于传统的氟硼二吡咯(BODIPY)荧光染料,设计合成了一种过氧化氢(H_(2)O_(2))激活型近红外光敏剂中位-N-(4-硼酸苄基)吡啶鎓盐取代的碘化双苯乙烯基氟硼二吡咯(FP-IBDP).FP-IBDP在乙腈中的吸收和发射波长均达到近红外区,最大吸收和发射波长分别为681 nm和740 nm,对应的荧光量子效率和单线态氧效率分别为0.01和0.09.在被H_(2)O_(2)激活后,FP-IBDP转变为IBDP,其在乙腈中的最大吸收和发射波长分别为661 nm和701 nm.与FP-IBDP相比,IBDP的荧光量子效率和单线态氧效率大幅提升,分别达到0.11和0.48.细胞水平的荧光影像实验表明FP-IBDP对癌细胞内的H_(2)O_(2)具有灵敏的响应,并能通过明显的荧光增强变化实现癌细胞与正常细胞的有效区分.活性氧检测实验证明FP-IBDP能够被癌细胞内过表达的H_(2)O_(2)激活,并能在660nm光照射下在癌细胞内产生单线态氧.噻唑蓝(MTT)比色法测试表明了FP-IBDP具有低的细胞暗毒性和好的生物相容性.细胞光毒性测试及活/死细胞染色标记实验则表明FP-IBDP对癌细胞具有更高的光毒性,而对正常细胞具有低的光损伤.细胞划痕实验进一步表明FP-IBDP在光照下能够有效抑制癌细胞增殖.此外,荧光共定位及溶酶体完整性检测实验表明FP-IBDP主要作用于细胞溶酶体,光照下产生的单线态氧通过破坏溶酶体导致溶酶体相关的细胞死亡.上述结果为氟硼二吡咯光敏剂FP-IBDP实现近红外光激发下荧光成像指导的光动力学治疗奠定了基础.
In this work,a borondipyrromethene(BODIPY)-based activatable photosensitizer FP-IBDP was designed and synthesized,which has absorption and emission wavelengths in the near infrared(NIR)region.The maximum absorption and emission of FP-IBDP are 681 nm and 740 nm in acetonitrile.The fluorescence quantum yield and singlet oxygen yield of FP-IBDP is 0.01 and 0.09,respectively.After activated by H_(2)O_(2),FP-IBDP was transformed to photosensitizer IBDP,which has maximum absorption and emission peak at 661 nm and 701 nm in acetonitrile.Compared with FP-IBDP,the fluorescence quantum yield and singlet oxygen yield of IBDP are much increased,up to 0.11 and 0.48 respectively.It is demonstrated that FP-IBDP can respond H_(2)O_(2) sensitively in cancer cells and has the ability to distinguish cancer cells from normal cells by a fluorescence enhancement way.Reactive oxygen species(ROS)detection indicated that FP-IBDP could be activated by the endogenous H_(2)O_(2) in cancer cells and produce highly toxic singlet oxygen under 660 nm light excitation with dichlorodihydrofluorescein diacetate(DCFH-DA)as ROS indicator.Tetrazolium(MTT)assay indicated that FP-IBDP has good biocompatibility and low dark toxicity to both cancer cells and normal cells,while phototoxicity test and living/dead cell double staining experiment proved that FP-IBDP has higher phototoxicity to cancer cells than to normal cells.Besides,wounding healing assay confirmed its good ability to inhibit cancer cell proliferation.Fluorescence localization and lysosome disruption assays further indicated that FP-IBDP was specifically located in lysosomes of living cells and the produced singlet oxygen could induce cancer cell death in a lysosome disruption associated pathway.These features are expected to lay good foundation for the application of FP-IBDP in imaging guided photodynamic therapy under NIR excitation.
作者
吕鑫
吴仪
张勃然
郭炜
Lv Xin;Wu Yi;Zhang Boran;Guo Wei(School of Chemistry and Chemical Engineering,Shanxi University,Taiyuan 030000,China)
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2023年第4期359-370,共12页
Acta Chimica Sinica
基金
国家自然科学基金(Nos.21778036,21877077)资助。
关键词
激活型光敏剂
近红外光
氟硼二吡咯光敏剂
光动力治疗
荧光成像
activatable photosensitizer
near infrared light
borondipyrromethene(BODIPY)photosensitizer
photodynamic therapy
fluorescence imaging
