Abstract
AbstractAptamers are emerging as promising molecular tools in cancer‐targeted theranostics. Improving their in vivo stability has been a critical issue in promoting clinical translation, but such efforts could lead to more serious side effects resulting from prolonged retention in healthy organs. To address this problem, we developed an environment‐responsive stabilization strategy for the selective enhancement of aptamer biostability in the tumor microenvironment (TME). Briefly, by means of the end extension of an ATP‐responsive protection (ARP) module, the designed aptamer could be protected from nuclease degradation through the specific incorporation of ATP. Based on our in vivo results, this ARP‐aptamer probe was effectively accumulated in tumors via aptamer‐based molecular recognition. It showed selectively prolonged tumor retention time, but rapid digestion in healthy organs. Our strategy should provide a new paradigm for the development of organ‐specific nucleic acid‐based imaging and therapeutic agents.
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