Pan Guang-Yu, Jia Hao-Ran, Zhu Ya-Xuan, Wang Ruo-Han, Wu Fu-Gen, Chen Zhan
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, P. R. China.
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109, United States.
ACS Biomater Sci Eng. 2017 Dec 11;3(12):3596-3606. doi: 10.1021/acsbiomaterials.7b00480. Epub 2017 Oct 12.
Because mitochondria are the key regulators for many cellular behaviors and are susceptible to hyperthermia and reactive oxygen species, mitochondria-specific reagents for simultaneous targeting, imaging, and treatment are highly desirable in cancer theranostics. Herein, we developed a mitochondria-targeted cyanine dye IR825-Cl, which possesses two separated excitation wavelength channels for both red fluorescence imaging and near-infrared (NIR) photothermal therapy (PTT). For imaging, IR825-Cl rapidly entered cells and selectively targeted mitochondria. Although IR825-Cl was completely quenched in water, interestingly, this dye had a turn-on response of red fluorescence (610 nm) in mitochondria under 552 nm excitation due to its polarity-responsive fluorescence emission. More interestingly, IR825-Cl realized the selective mitochondrial staining of cancer cells over normal cells and thus served as an ideal fluorescent probe for identifying cancer cells in normal tissues, which is extremely beneficial for cancer theranostics. For PTT, we demonstrated that under 808 nm NIR laser irradiation, this dye efficiently converted optical energy into heat, realizing mitochondria-targeted photothermal cancer therapy. Collectively, this molecule realized both high fluorescence emission (quantum yield > 43%) and effective light-to-heat conversion (17.4%), enabling its applications for wash-free fluorescence imaging for mitochondria and highly efficient fluorescence imaging-guided PTT.
由于线粒体是许多细胞行为的关键调节因子，且易受高温和活性氧的影响，因此在癌症诊疗中非常需要能够同时实现靶向、成像和治疗的线粒体特异性试剂。在此，我们开发了一种线粒体靶向花菁染料IR825-Cl，它具有两个分离的激发波长通道，可用于红色荧光成像和近红外（NIR）光热疗法（PTT）。用于成像时，IR825-Cl能快速进入细胞并选择性地靶向线粒体。虽然IR825-Cl在水中完全淬灭，但有趣的是，由于其极性响应荧光发射，该染料在552 nm激发下在线粒体中具有开启的红色荧光（610 nm）响应。更有趣的是，IR825-Cl实现了癌细胞相对于正常细胞的选择性线粒体染色，因此可作为在正常组织中识别癌细胞的理想荧光探针，这对癌症诊疗极为有利。用于PTT时，我们证明在808 nm近红外激光照射下，该染料能有效地将光能转化为热能，实现线粒体靶向光热癌症治疗。总体而言，该分子实现了高荧光发射（量子产率>43%）和有效的光热转换（17.4%），使其可用于线粒体的免洗荧光成像以及高效的荧光成像引导PTT。
