State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China.
J Med Chem. 2024 Jan 11;67(1):467-478. doi: 10.1021/acs.jmedchem.3c01677. Epub 2023 Dec 26.
Subcellular organelle mitochondria are becoming a key player and a driver of cancer. Mitochondrial targeting phototheranostics has attracted increasing attention for precise cancer therapy. However, those phototheranostic systems still face great challenges, including complex and multiple components, light scattering, and insufficient therapeutic efficacy. Herein, a molecular fluorophore IR-TPP-1100 was tactfully designed by molecular engineering for mitochondria-targeted fluorescence imaging-guided phototherapy in the second near-infrared window (NIR-II). IR-TPP-1100 not only exhibited prominent photophysical properties and high photothermal conversion efficiency but also achieved excellent mitochondria-targeting ability. The mitochondria-targeting IR-TPP-1100 enabled NIR-II fluorescence and photoacoustic dual-modality imaging of mitochondria at the organism level. Moreover, it integrated photothermal and photodynamic therapy, obtaining remarkable tumor therapeutic efficacy by inducing mitochondrial apoptosis. These results indicate that IR-TPP-1100 has great potential for precise cancer therapy and provides a promising strategy for developing mitochondria-targeting NIR-II phototheranostic agents.
细胞内细胞器线粒体正在成为癌症的关键参与者和驱动因素。线粒体靶向光热治疗已经引起了人们对精确癌症治疗的越来越多的关注。然而，这些光热治疗系统仍然面临着巨大的挑战，包括复杂和多种成分、光散射以及治疗效果不足。在这里，通过分子工程巧妙地设计了一种分子荧光团 IR-TPP-1100，用于在近红外二区（NIR-II）进行线粒体靶向荧光成像引导的光疗。IR-TPP-1100 不仅表现出突出的光物理性质和高光热转换效率，而且还实现了优异的线粒体靶向能力。线粒体靶向的 IR-TPP-1100 能够在机体水平上实现线粒体的近红外二区荧光和光声双模式成像。此外，它集成了光热和光动力治疗，通过诱导线粒体凋亡获得了显著的肿瘤治疗效果。这些结果表明，IR-TPP-1100 具有精确癌症治疗的巨大潜力，并为开发线粒体靶向 NIR-II 光热治疗剂提供了一种有前途的策略。
