posted on 2024-01-19, 21:04authored byJing Fang, Qingzhu Liu, Yaling Liu, Ke Li, Ling Qiu, Hongjie Xi, Shuyue Cai, Pei Zou, Jianguo Lin
Improving
the retention of small-molecule-based therapeutic agents
in tumors is crucial to achieve precise diagnosis and effective therapy
of cancer. Herein, we propose a β-galactosidase (β-Gal)-activated
and red light-induced RNA modification (GALIRM) strategy for prolonged
tumor imaging. A β-Gal-activatable near-infrared (NIR) fluorescence
(FL) and positron emission tomography (PET) bimodal probe 68Ga-NOTA-FCG consists of a triaaza triacetic acid chelator NOTA for 68Ga-labeling, a β-Gal-activated photosensitizer CyGal,
and a singlet oxygen (1O2)-susceptible furan
group for RNA modification. Studies have demonstrated that the probe
emits an activated NIR FL signal upon cleavage by endogenous β-Gal
overexpressed in the lysosomes, which is combined with the PET imaging
signal of 68Ga allowing for highly sensitive imaging of
ovarian cancer. Moreover, the capability of 68Ga-NOTA-FCG
generating 1O2 under 690 nm illumination could
be simultaneously unlocked, which can trigger the covalent cross-linking
between furan and nucleotides of cytoplasmic RNAs. The formation of
the probe-RNA conjugate can effectively prevent exocytosis and prolong
retention of the probe in tumors. We thus believe that this GALIRM
strategy may provide entirely new insights into long-term tumor imaging
and efficient tumor treatment.