化学学报 ›› 2022, Vol. 80 ›› Issue (3): 291-296.DOI: 10.6023/A21120544 上一篇    下一篇

研究论文

水溶性IR-780聚合物用于线粒体靶向的光动力治疗

李嫣然a,c, 王子贵b,c, 汤朝晖a,c,*()   

  1. a 中国科学院长春应用化学研究所 中国科学院生态环境高分子材料重点实验室 长春 130022
    b 中国科学院长春应用化学研究所 高分子物理与化学重点实验室 长春 130022
    c 中国科学技术大学 应用化学与工程学院 合肥 230026
  • 投稿日期:2021-12-03 发布日期:2022-01-07
  • 通讯作者: 汤朝晖
  • 作者简介:
    庆祝中国科学院青年创新促进会十年华诞.
  • 基金资助:
    国家自然科学基金(52025035); 国家自然科学基金(51873206)

Water Soluble IR-780 Polymer for Mitochondria-Targeted Photodynamic Therapy

Yanran Lia,c, Zigui Wangb,c, Zhaohui Tanga,c()   

  1. a Key Laboratory of Polymer Ecomaterials, Chinese Academy of Sciences, Changchun Institute of Applied Chemistry of Chinese Academy of Sciences, Changchun 130022
    b State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry of Chinese Academy of Sciences, Changchun 130022
    c College of Applied Chemistry and Engineering, University of Science and Technology of China, Heifei 230026
  • Received:2021-12-03 Published:2022-01-07
  • Contact: Zhaohui Tang
  • About author:
    Dedicated to the 10th anniversary of the Youth Innovation Promotion Association, CAS.
  • Supported by:
    National Natural Science Foundation of China(52025035); National Natural Science Foundation of China(51873206)

11-氯-1,1'-二正丙基-3,3,3',3'-四甲基-10,12-三亚甲基吲哚三碳花青碘盐(IR-780)被具有较强组织穿透能力的近红外光照射后, 能快速高效地产生活性氧, 导致细胞死亡, 可用于光动力治疗. 但是IR-780的水溶性差, 这极大限制了其生物医学应用. 基于此我们设计合成了可高效靶向线粒体的水溶性IR-780聚合物Poly-IR, Poly-IR在水中自组装成为纳米粒子. Poly-IR纳米粒子受近红外光激活后, 在肿瘤细胞内外均能快速高效地产生活性氧, 并且该纳米粒子能够在线粒体中富集, 受近红外光的激发后产生的活性氧能够破坏线粒体, 导致线粒体膜电位降低. 细胞毒性、活死细胞染色及凋亡实验结果也进一步证明, 该纳米粒子在近红外光照下能够有效地抑制肿瘤细胞的增殖. 本体系为靶向线粒体的光动力治疗肿瘤领域拓展了思路.

关键词: 光动力疗法, 活性氧, IR-780, 线粒体靶向, 纳米粒子

11-Chloro-1,1'-di-n-propyl-3,3,3',3'-tetramethyl-10,12-trimethyleneindatricarbocyanine iodide (IR-780) is a near infrared (NIR) photosensitizer for cancer treatment. Under NIR irradiation, IR-780 efficiently generates singlet oxygen or other reactive oxygen species (ROS) in lesion position that ultimately cause cell apoptosis and necrosis. However, biomedical application of IR-780 was limited by its poor water solubility. In this work, we designed a water-soluble IR-780 polymer (Poly-IR) for mitochondria-targeted photodynamic therapy via condensation polymerization. The results of dynamic light scattering (DLS) and transmission electron microscope (TEM) displayed that Poly-IR was self-assembled into nanoparticles in water. And ROS detection experiments demonstrated that Poly-IR quickly and efficiently generated ROS under NIR irradiation in solution and cells. The cellular distribution of the Poly-IR was monitored by confocal laser scanning microscopy (CLSM). Colocalization experiments with mitochondrial stain revealed a high degree of colocalization between Poly-IR and mitochondria, which illustrated that Poly-IR selectively accumulated in mitochondria. Furthermore, we explored the photodamages of Poly-IR to mitochondria through monitoring the change of mitochondrial membrane potential that was stained by JC-1 probe. In the dark, red fluorescence emerged with Poly-IR treated A549 cells. Under NIR irradiation, the red fluorescence was disappeared and green fluorescence was generated in Poly-IR treated cells, which confirmed the photodamage of Poly-IR to mitochondria. The cytotoxicity of Poly-IR was measured by MTT assay (MTT=3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide). The IC50 values of Poly-IR for A549 cells and MCF-7 cells were 9.13 and 10.98 μg/mL respectively in the dark. At the same time, the IC50 values of Poly-IR for A549 cells and MCF-7 cells were 4.57 and 0.22 μg/mL respectively under NIR irradiation. The cytotoxicity of Poly-IR for MCF-7 cells treated with NIR exposure was significantly increased 50 times compared to without irradiation. Live/dead cell staining experiments also verified that Poly-IR had more phototoxicity. Meanwhile, cytotoxicity on tumor cells was also detected by flow cytometry apoptosis assay according to the typical Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) double staining principle. These results suggested that Poly-IR promoted tumor cells apoptosis under near-IR irradiation, which expanded ideas in mi-tochondria-targeted photodynamic therapy in cancer treatment.

Key words: photodynamic therapy, reactive oxygen species (ROS), IR-780, mitochondria-target, nanoparticles