Zhu Junfei, He Gang, Chen Peng-Hang, Zhang Yajie, Zhang Yafei, Lei Shan, Zhang Yu, Li Meng, Huang Peng, Lin Jing
Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.
Research (Wash D C). 2023;6:0061. doi: 10.34133/research.0061. Epub 2023 Feb 27.
Heptamethine cyanines (Cy7) are one of the most important dyes in bioimaging and phototherapy, but they often suffer from poor photostability or limited photothermal conversion efficiency. Here, a facile molecular engineering approach to regulating the photophysical properties of Cy7 by metal ions is demonstrated. By innovatively modifying the nitrogen with functional groups, a novel terpyridine-grafted nitrogen-terminated Cy7 scaffold (denoted as CydtPy) was synthesized and exhibited tunable photophysical properties when chelating with various metal ions (Mn, Fe, etc.). In comparison with metal-ion-free PEGylated CydtPy (LET-11), Mn-chelated LET-11 (namely, LET-11-Mn) exhibited the increased fluorescence emission intensity, and Fe-chelated LET-11 (namely, LET-11-Fe) showed the enhanced photostability with ~2-fold increase in photothermal conversion efficiency. By simply switching the chelated metal ion species, LET-11-Mn or LET-11-Fe could be used for near-infrared fluorescence imaging, magnetic resonance imaging, or photoacoustic imaging. Furthermore, LET-11-Fe displayed superior synergistic efficacy of photothermal therapy and chemodynamic therapy both in vitro and in vivo. This work not only provides a new strategy for regulating the photophysical properties of cyanine dyes but also establishes a versatile nanoplatform for cancer theranostics.
七甲川花菁（Cy7）是生物成像和光疗中最重要的染料之一，但它们常常存在光稳定性差或光热转换效率有限的问题。在此，展示了一种通过金属离子调节Cy7光物理性质的简便分子工程方法。通过用官能团创新性地修饰氮原子，合成了一种新型的接枝有三联吡啶的氮端基Cy7支架（记为CydtPy），并且在与各种金属离子（锰、铁等）螯合时表现出可调的光物理性质。与不含金属离子的聚乙二醇化CydtPy（LET-11）相比，锰螯合的LET-11（即LET-11-Mn）表现出增强的荧光发射强度，而铁螯合的LET-11（即LET-11-Fe）显示出增强的光稳定性，光热转换效率提高了约2倍。通过简单地切换螯合的金属离子种类，LET-11-Mn或LET-11-Fe可用于近红外荧光成像、磁共振成像或光声成像。此外，LET-11-Fe在体外和体内均表现出光热疗法和化学动力疗法的优异协同疗效。这项工作不仅为调节花菁染料的光物理性质提供了一种新策略，还建立了一种用于癌症诊疗的多功能纳米平台。
