19F-magnetic resonance imaging (MRI) is of great significance for noninvasive imaging and detection of various diseases. However, the main obstacle in the application of 19F-MRI agents stems from the unmet signal sensitivity due to the poor water solubility and restricted mobility of segments with high number of fluorine atoms. Herein, we report a kind of intracellular reducing microenvironment-induced amino-activatable 19F-MRI nanoprobe, which can be used for specific imaging of biothiols. In principle, the nanoprobe has an initial architecture of hydrophobic core, where the trifluoromethyl-containing segments are compactly packed and 19F NMR/MRI signals are quenched ("OFF" state). Upon encountering sulfydryl, the strong electron-withdrawing 2,4-dinitrobenzenesulfonyl groups are excised to recover secondary amino groups, whose pKa is proved to be 7.21. As a consequence, the molecular weight loss of the hydrophobic segment and the protonation of amino groups induce significant disturbance of hydrophilic/hydrophobic balance, leading to the disassembly of the nanoprobes and regain of spin-spin relaxation and 19F NMR/MRI signals ("ON" state, T2 up to 296 ± 5.3 ms). This nanoprobe shows high sensitivity and selectivity to biothiols, enabling intracellular and intratumoral imaging of glutathione. Our study not only provides a new nanoprobe candidate for biothiols imaging in vivo but also a promising strategy for the molecular design of real water-soluble and highly sensitive 19F-MRI nanoprobes.
Bibliographical noteFunding Information:
This work was financially supported by the National Natural Science Foundation of China (31670977, 51203189, 51703246, and 81220108015), Tianjin Natural Science Foundation (16JCQNJC14200 and 17JCQNJC13800), Science and Technology Support Program of Tianjin (no. 15RCGFSY00146) and CAMS Innovation Fund for Medical Sciences (CIFMS, 2016-I2M-3-022), Natural Science Foundation key project (31630027 and 31430031), and National Distinguished Young Scholars grant (31225009). We also appreciate the support by the “Strategic Priority Research Program” of the Chinese Academy of Sciences, grant no. XDA09030301 and support by the external cooperation program of BIC, Chinese Academy of Science, grant no. 121D11KYSB20130006.
- amino activation
- reducing microenvironment
- thiol imaging