Shao Nannan, Qi Yanxin, Lu Hongtong, He Dongyun, Li Bin, Huang Yubin
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
University of Science and Technology of China, Hefei 230026, P. R. China.
ACS Biomater Sci Eng. 2019 Feb 11;5(2):795-804. doi: 10.1021/acsbiomaterials.8b01558. Epub 2019 Jan 7.
The development of near-infrared (NIR) dyes with desirable photophysical characteristics for tumor therapy is highly expected at present. In this report, IR-780 iodide was loaded by the mercaptopropionic acid grafted poly(ethylene glycol)--poly(ε-caprolactone)--poly(allyl glycidyl ether) [mPEG-PCL-PAGE (MPA)] copolymer to form nanomicelles (IR-780@TBMPA) in aqueous solution. On account of the hydrophobic and electrostatic interaction between mPEG-PCL-PAGE (MPA) and IR-780, the IR-780@TBMPA micelle was structurally stable with improved solubility, light stability and biocompatibility. The encapsulation of IR-780 indicated no influence on its original physicochemical property, showing good optical and thermal characteristics. The drug-loaded micelles had appropriate microscopic size for endocytosis, displaying significant cytotoxicity to HeLa cells under NIR laser irradiation. In addition, the phototoxicity generated by photothermal and photodynamic effect of IR-780@TBMPA under 808 nm laser irradiation was also investigated by reactive oxygen species (ROS) detection and flow cytometry. Furthermore, the superior accumulation of IR-780@TBMPA in tumor tissues provided sufficient hyperthermia to kill tumor cells, indicating its potential in cancer clinical therapy.
目前，人们迫切期望开发出具有理想光物理特性用于肿瘤治疗的近红外（NIR）染料。在本报告中，通过巯基丙酸接枝的聚（乙二醇）-聚（ε-己内酯）-聚（烯丙基缩水甘油醚）[mPEG-PCL-PAGE（MPA）]共聚物负载碘化IR-780，在水溶液中形成纳米胶束（IR-780@TBMPA）。由于mPEG-PCL-PAGE（MPA）与IR-780之间的疏水和静电相互作用，IR-780@TBMPA胶束结构稳定，溶解性、光稳定性和生物相容性均得到改善。IR-780的包封对其原始物理化学性质没有影响，显示出良好的光学和热学特性。载药胶束具有适合内吞作用的微观尺寸，在近红外激光照射下对HeLa细胞显示出显著的细胞毒性。此外，还通过活性氧（ROS）检测和流式细胞术研究了IR-780@TBMPA在808 nm激光照射下的光热和光动力效应产生的光毒性。此外，IR-780@TBMPA在肿瘤组织中的优异蓄积提供了足够的热疗来杀死肿瘤细胞，表明其在癌症临床治疗中的潜力。
