Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 141, Issue 46, Pages 18421-18427Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.9b05063
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Funding
- NSFC [21974040, 61527806, 21804037]
- Science and Technology Project of Hunan Province [2017XK2103]
- State Key Laboratory of Chemo/Biosensing and Chemometrics
- Fundamental Research Funds for the Central Universities
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Aptamers and antibodies, as molecular recognition probes, play critical roles in cancer diagnosis and therapy. However, their recognition ability is based on target overexpression in disease cells, not target exclusivity, which can cause on-target off-tumor effects. To address the limitation, we herein report a novel strategy to develop a conditional aptamer conjugate which recognizes its cell surface target, but only after selective activation, as determined by characteristics of the disease microenvironment, which, in our model, involve tumor hypoxia. This conditional aptamer is the result of conjugating the aptamer with PEG(5000)-azobenzene-NHS, which is responsive to hypoxia, here acting as a caging moiety of conditional recognition. More specifically, the caging moiety is unresponsive in the intact conjugate and prevents target recognition. However, in the presence of sodium dithionite or hypoxia (<0.1% O-2) or in the tumor microenvironment, the caging moiety responds by allowing conditional recognition of the cell-surface target, thereby reducing the chance of on-target off-tumor effects. It is also confirmed that the strategy can be used for developing a conditional antibody. Therefore, this study demonstrates an efficient strategy by which to develop aptamer/antibody-based diagnostic probes and therapeutic drugs for cancers with a unique hypoxic microenvironment.
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