The design and synthesis of near-infrared (NIR) emissive fluorophores for the imaging of organelles and photodynamic therapy have received enormous attention. Hence, the development of NIR emissive fluorophores for high-fidelity lysosome targeting, two-photon fluorescence imaging, and the inducing of photo-triggered cancer-cell apoptosis is highly desirable. In this study, a novel lysosome-targeting two-photon fluorescent photosensitizer (TTRh-CN) is prepared and comprehensively investigated. TTRh-CN demonstrates near-infrared (NIR) emission, good biocompatibility, and superior photostability, and it can act as a two-photon fluorescent agent for the clear visualization of living cells and the vascular system within tissue, with deep-tissue penetration abilities. Furthermore, TTRh-CN can efficiently produce ROS in conjunction with lysosomes in situ upon light irradiation, which can damage lysosomes, up-regulate LC3 and Beclin1, increase BAX release, and induce cell apoptosis. The efficacy of TTRh-CN as a photosensitizer is explored in vivo. All these results confirm that TTRh-CN can serve as a potential platform for the two-photon fluorescence imaging of cells/tissue and for organelle-specific photodynamic therapy.

中文翻译：

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溶酶体靶向NIR光敏剂，用于光动力疗法和双光子荧光成像

用于细胞器成像和光动力疗法的近红外（NIR）发射荧光团的设计和合成受到了广泛的关注。因此，非常需要开发用于高保真性溶酶体靶向，双光子荧光成像以及诱导光触发的癌细胞凋亡的NIR发射荧光团。在这项研究中，一种新型的靶向溶酶体的双光子荧光光敏剂（TTRh-CN）被制备并进行了全面的研究。TTRh-CN具有近红外（NIR）发射，良好的生物相容性和优异的光稳定性，它可以用作双光子荧光剂，以清晰地观察组织中的活细胞和血管系统，并具有深层组织穿透能力。此外，TTRh-CN可以与溶酶体一起有效产生ROS在光照射下原位，可损坏溶酶体，上调LC3和Beclin1，增加BAX释放，并诱导细胞凋亡。在体内探索了TTRh-CN作为光敏剂的功效。所有这些结果证实，TTRh-CN可以作为细胞/组织的双光子荧光成像以及细胞器特异性光动力疗法的潜在平台。