Journal
ANALYTICAL CHEMISTRY
Volume 91, Issue 14, Pages 9154-9160Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.9b01828
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [21735002, 21575037, 21521063, 21675046, 21778016, 21775036]
Ask authors/readers for more resources
Activatable aptamer probes (AAPs) are promising in molecular imaging of tumors, but the reported shape-switching dependent AAPs are still challenged by unsatisfied noise suppression, poor stability, and sophisticated sequence design. To address the problem, we constructed a pH-activatable aptamer probe (pH-AAP) by utilizing an acid-labile acetal linker as the responsive element to be fused with a tumor-targeted aptamer. Specifically, a CyS-labeled aptamer was connected with the quencher BHQ2 through the acetal group, thus generating pH-AAP with quenched fluorescence. Due to the stable proximity of CyS to BHQ2, pH-AAP was found to have ultralow background with a quenching efficiency as high as 98%. In comparison with shape-switching-dependent AAPs, the noise suppression of pH-AAP was well maintained for a much longer time in both serum and mouse body, thus showing a robust fluorescence stability. By a combination of the fluorescence recovery induced by acid hydrolysis of acetal linkers and the tumor-targeted recognition of aptamers, pH-AAP could either specifically anchor the extracellular pH-activated signals on the target cell surface in an acidic tumor microenvironment or be activated by acidic lysosomes after it was internalized into target cells. As proof of concept, in vitro evaluation and in vivo imaging of A549 lung cancer cells were performed by using S6 aptamer as a demonstration. It was indicated that pH-AAP realized washing-free, bispecific, and contrast-enhanced tumor imaging. The strategy is simple and free of sequence modification, which promises to provide a universal platform for sensitive and precise tumor diagnosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available