Recently, the research team from the Innovation Academy for Precision Measurement Science and Technology (APM) has made a breakthrough in the field of magnetic resonance contrast agent development. They proposed a convenient and efficient "ion-pairing" strategy. This strategy can rapidly transform traditional cationic photosensitizers into novel molecules with ¹⁹F magnetic resonance imaging (¹⁹F MRI) functionality by introducing bulky, highly fluorinated anions, providing a brand-new approach for constructing a high-sensitivity, multimodal tumor diagnosis and treatment platform. The relevant research findings have been published in the journal Small.
Due to its advantages such as the absence of endogenous background signal interference and the capability of quantitative imaging, ¹⁹F MRI has garnered significant attention in the field of precision medicine. It has been successfully applied in photosensitizer-based multimodal diagnosis and treatment systems, enabling precise in-vivo tracking of photosensitizers and providing treatment guidance. However, at present, multimodal imaging contrast agents generally suffer from issues such as cumbersome synthesis or complex compositions, which restrict their application promotion and clinical translation.
To address this issue, the research team innovatively adopted the ion-pairing strategy. They paired the commercially available cationic near-infrared photosensitizer IR780 with the [Al{OC(CF₃)₃}₄]⁻ anion containing 36 magnetically equivalent fluorine atoms, successfully constructing the polyfluorinated fluorescent molecule F36IR. This marks the first time that this strategy has been applied in the development of ¹⁹F MRI contrast agents. This strategy not only endows the photosensitizer with a strong and single ¹⁹F NMR signal, but also effectively suppresses the fluorescence quenching (ACQ) caused by molecular aggregation through the large steric hindrance effect, thereby enhancing its near-infrared fluorescence performance and photostability. Additionally, this ion-pairing strategy exhibits good versatility. It can achieve rapid pairing with various cationic dyes such as thiazole orange, methylene blue, and IR1061. With only 30 seconds of ultrasonic treatment, it can endow conventional fluorescent molecules with ¹⁹F MRI functionality and improve their fluorescence performance. There is no need for cumbersome organic synthesis modifications, significantly enhancing the construction efficiency of multimodal contrast molecules (Figure 1).
The ion-pairing strategy enables rapid fluorination of fluorescent molecules, enhances their fluorescence performance, and confers ¹⁹F MRI functionality
This study proposes an efficient strategy that enables the integration of multiple functions without altering the molecular framework. It opens up a new path for the development of ¹⁹F MRI contrast agents, provides support for the rapid construction of multimodal theranostic systems, and shows broad application prospects.
The research findings were published in the journal Small under the title "Enabling ¹⁹F MRI and Boosting Phototherapy through Facile Counterion Pairing of Photosensitizers". Ph.D. student PENG Xingxing, Associate Research Fellow LI Yu, and Postdoctoral Fellow ZHU Lijun from APM are the co-first authors of the article, while Research Fellow JIANG Zhongxing serves as the corresponding author.
This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences and the National Natural Science Foundation of China.
Link to the article: https://doi.org/10.1002/smll.202505497