[Synthesis of BODIPY photosensitizers and their photodynamic effect on cancer cells]

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2017 Mar 25;46(2):118-126. doi: 10.3785/j.issn.1008-9292.2017.04.02.
[Article in Chinese]

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.

目的: 以细菌外膜囊泡(OMV)结合三嵌段聚合物普朗尼克F127(PEO 100-PPO 65-PEO 100),构建能够有效促进巨噬细胞分泌抗肿瘤细胞因子的纳米载药体系OMV-F127。

方法: 培养减毒沙门菌,用超滤离心法与超声破碎法提取OMV,机械挤压法制得OMV-F127;蛋白质定量试剂盒和SDS-PAGE法检测OMV的蛋白含量和成分;荧光显微镜、透射电镜、动态光学散射法检测OMV-F127形态学特征、粒径、电位及其稳定性;以小鼠巨噬细胞RAW246.7为细胞模型,ELISA检测OMV-F127对抗肿瘤细胞因子的分泌作用。

结果: 两种方法成功提取到减毒沙门菌的OMV,其蛋白质总量分别为2.8 mg/mL和2.7 mg/mL。成功制备OMV-F127且含有OMV的标志蛋白OmpF/C。OMV为纳米级囊泡结构,F127以及OMV-F127为球形纳米颗粒。OMV、F127、OMV-F127颗粒平均直径分别为(72±2)nm、(90±3)nm、(92±2)nm。OMV-F127能促进抗肿瘤细胞因子IF-12、α-TNF、γ干扰素的分泌。

结论: 基于细菌OMV的纳米载体OMV-F127能够有效促进巨噬细胞分泌抗肿瘤细胞因子,具有免疫调节作用。

MeSH terms

  • Animals
  • Boron Compounds / chemistry
  • Cell Line, Tumor
  • Glioma
  • Photochemotherapy*
  • Photosensitizing Agents* / chemical synthesis
  • Photosensitizing Agents* / pharmacology
  • Rats
  • Reactive Oxygen Species / metabolism
  • Spectroscopy, Fourier Transform Infrared*

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Photosensitizing Agents
  • Reactive Oxygen Species

Grants and funding

国家自然科学基金(21374098)