摘要
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.
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 IC;values of Poly-IR for A549 cells and MCF-7 cells were 9.13 and 10.98μg/mL respectively in the dark. At the same time, the IC;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 mitochondria-targeted photodynamic therapy in cancer treatment.
作者
李嫣然
王子贵
汤朝晖
Li Yanran;Wang Zigui;Tang Zhaohui(Key Laboratory of Polymer Ecomaterials,Chinese Academy of Sciences,Changchun Institute of Applied Chemistry of Chinese Academy of Sciences,Changchun 130022;State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry of Chinese Academy of Sciences,Changchun 130022;College of Applied Chemistry and Engineering,University of Science and Technology of China,Heifei 230026)
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2022年第3期291-296,共6页
Acta Chimica Sinica
基金
国家自然科学基金(Nos.52025035,51873206)资助项目。
关键词
光动力疗法
活性氧
IR-780
线粒体靶向
纳米粒子
photodynamic therapy
reactive oxygen species(ROS)
IR-780
mitochondria-target
nanoparticles
作者简介
汤朝晖,E-mail:ztang@ciac.ac.cn。
